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LSD

C20H25N30

Lysergic acid diethylamide

Lysergic acid diethylamide, commonly referred to as "LSD" or "Acid" is regarded as one of the most potent psychedelic substances. It takes a mere 100 micrograms (100 millionths of a gram) of this substance to produce strong and long lasting psychoactive effects.

When ingested, LSD acts as a 5-HT (serotonin) receptor antagonist, thereby affecting the cognitive functions which emanate from the pre-frontal cortex - the area that regulates our thought-processes, behaviors, and decision-making capabilities. 

It's for this reason that LSD has been linked to the optimization of productivity and is quickly becoming regarded as one of the most valuable nootropics of the 21st century. 

Overview

“Taking LSD was a profound experience, one of the most important things in my life. LSD shows you that there’s another side to the coin, and you can’t remember it when it wears off, but you know it. It reinforced my sense of what was important — creating great things instead of making money, putting things back into the stream of history and of human consciousness as much as I could.”
― Steve Jobs

A vivid history

Many of us have heard the story of how lysergic acid diethylamide (LSD) had first been synthesized — Swiss chemist Albert Hofmann and his infamous bicycle day which we now celebrate on the 19th of every April — but few of us have come to appreciate LSD’s significant influence on countless areas of our socio-political culture. 

Our collective curiosity into examining the effects of this peculiar substance have been exemplified in both enlightening and nefarious ways — from the enthusiastic studies of Timothy Leary and the hippie counterculture of the 1960s to the CIA’s experimentation with LSD (and Project MK-Ultra) the decade prior.

Acid, as it’s become colloquially regarded, has a long and complex history, infusing North American culture with the same kinds of effects it seems to produce in the mind of its consumer: intensified thoughts and perceptions, expanded cognitive activity, existential contemplation.

And it seems we’re only on the cusp of understanding its true potential. 

Nature or nurture?

One of the most fascinating aspects of LSD’s history regards its transition from a naturally-occurring derivative (from ergot — a fungal growth common to grains) to the synthesized product we use today.

Its extreme potency is a testament to the true power that it holds, in even the smallest amounts. It’s odorless, colorless and tasteless nature allows it to be easily infused into any medium — tablet, capsule, powder or, most popular, either suspended in liquid or ‘blotted’ onto paper.

Effects are typically felt within the first half hour to an hour, causing sensory distortion, more vivid perceptional experiences, synesthesia and variable degrees of hallucination.

Notable amongst its core characteristics are the duration of its effect on the mind, sometimes lasting up to 20 hours. Despite the heavier effect, micro-dosing has become an increasingly popular method by which LSD is consumed, offering a manageable regiment of steady effects that are regarded to be especially conducive towards efforts of self-improvement or focus-habituation. 

 

Psychedelic 2.0

Perhaps most appealing is LSD’s status as the prototypical psychedelic — a synthesized compound of utility that offers to increase cognitive activity and performance. Its effects are more stimulatory in nature as it binds to dopamine receptors in addition to serotonin receptors, offering a more fast-paced experience than other psychedelics like psilocybin. 

For these reasons, LSD has become synonymous with productivity and self-optimization, from the tech-savvy crowds of Silicon Valley to the financiers and traders of Wall Street. 

Though it should be regarded that LSD still offers a capacity for reverential insight, as well as a tremendous prospect for therapeutic endeavors, becoming a mechanism of choice for countless clinicians and pharmacologists across North America. 

Compounded with concepts like neuroplasticity or practices like meditation, LSD offers a dramatic expansion of our horizons when it comes to our conscious potential, from efficiency to understanding. 

As our relationship with LSD evolves amidst greater understanding and acceptance, the true potential of this powerful substance is finally being fully realized. Though as the current reverberations flow through so many domains of our existence — from therapy couches to workspaces to easels — we’ve yet to reach the peak of its potent effect on our culture. 

DOSAGE & Experience

Due to its extreme potency, LSD is considered to be rather unpredictable in intensity, as even the most miniscule of dosage variations can induce considerably different trips; combined with the setting of an experience and a number of other variables (i.e. purpose, frame of mind), LSD is considered an extremely versatile psychedelic, illuminating the fact that hallucinogens should always be perceived as extremely subjective commodities.

On the lower end of the scale, whereby a consumer can experience a mild or threshold experience, 10ug to 50ug will often prompt some level of change to sensory perception and a very subtle sense of mood elevation, along with an array of cognitive effects that can be likened to a strong cup of coffee. A microdose range will typically fall somewhere between 15ug to 35ug and is often associated with boosts to mental efficacy, increased creativity, improved cognitive function and heightened focus. 

On the moderate range of the scale, at about 50ug to 200ug, a more substantial experience can be felt whereby hallucinations will occur alongside a distortion of sensory perceptions, time, and emotion. Ego-dissolution, identity contemplation, existential commiseration are all normal happenstance, with effects peaking within 1-2 hours and lasting 4-8 hours in total.

On the higher end of the scale of 200ug +, experiences can vary depending on tolerance, setting, and expectation, through very strong hallucinations are common, alongside substantial distortions of time, sensory experience, auditory perception and vision. Rationality and self-identity is usually compromised, as is a sense of control. For those unfamiliar with psychedelics, panic may occur during this temporal disassociation with reality. Some level of psychosis (not necessarily unpleasant) will be induced during the intense period that can last up to 12 hours. 

Pharmacology

Upon ingestion, LSD acts as a serotonin receptor activator, disrupting the regulation of serotonin levels (and increasing them) in the brain. LSD will mostly combine with the receptors associated with cognitive function within the pre-frontal cortex - that which regulates decision making and behaviour, affecting the brains processing ability. Many will consider this to improve mental function and thus utilize LSD as a tool towards mental optimization. 

While the comprehensive pharmacology of LSD is not yet fully understood due to the inherent complexity of its mechanisms of action, LSD is well tolerated by the physiology of the brain, allowing psychological reactions to be relatively controllable. 

New applications are being considered in its therapeutic ability to treat depression and emotional dysfunction, cluster headaches and a range of neurological symptomology, as well as psychological management of the terminally ill. 

Pop Culture

Studies 

Since its initial synthesis in 1938, LSD has been one of the most popular psychedelics on the scene, seeing its popularity exponentiated through its dual-headed use as both a nefarious military weapon and a creative inspiration to beatnik artists. 

Today, Hollywood has no hard time creating fictional stories based on non-fictional circumstances relating to the employment of LSD throughout the mid 21st century, as many blockbuster hits make reference to initiatives such as MKUltra and Operation Paperclip. 

More notable are the sponsorships of this psychedelic by popular names throughout all spectrums of Western culture - from artists like the Beatles, authors like Aldous Huxley and Harvard professors like Tim Leary, the latter of which can be most thanked for shaping our modern understanding of this powerful substance.

LSD's uncanny ability to distort sensory perception and allow for an experience unlike any other have proved pivotal in our fascination with the expansion of consciousness and have motivated countless artists and researchers alike to promote this iconic substance. 

Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission

 

Published February 2nd, 2021 by Roland Danila De Gregoria et. al. 

 

About: This study sought to examine whether microdoses of LSD could offer the potential to promote various levels of social behaviour. Administering low doses of LSD to mice, the authors detailed the prosocial effects of LSD as it influences various receptors relating to social behaviour. Specifically, repeated doses of LSD served to excite AMPA and 5-HT2A receptors by increasing the phosphorylation of a protein (mTORC1) that modulates social behaviour. 

 

Excerpt: "It is noteworthy that the behavioral outcomes documented in our study were obtained with a relatively low dose of LSD, compared to previous studies in animals (100 to 200 µg/kg) and humans... our study unveils a mechanism contributing to the prosocial effects of LSD, through the stimulation of 5-HT2A and AMPA receptors and the activation of the mTORC1 pathway in excitatory neurons."

 

Link: https://www.pnas.org/content/118/5/e2020705118

Twenty percent better with 20 micrograms? A qualitative study of psychedelic microdosing self-rapports and discussions on YouTube

Published November 28th, 2019 by Martin Andersson and Anette Kjellgren

 

About: Building atop the trending practice of microdosing LSD, the authors of this study sought to qualitatively analyze social media accounts, cultivating data and assessing it through a method that the authors refer to as 'inductive thematic analysis'. They conclude that microdosing can provide similar benefits to full-dose therapeutic interventions with less risk of adverse reactions that are related to experiences with higher doses. 

 

Excerpt: "Social media and internet discussion forums have played a substantial role in the growing visibility of the microdosing phenomenon...  In recent years, the microdosing forum of Reddit.com has annually doubled the number of subscribers... Self-reporting and sharing of drug experiences in online text-based drug forums have proved to be an expedient source of qualitative data for research... A process of augmented self-reflection was often seen as central to the microdosing practice. The microdosers gave extensive descriptions of thoughtful insights and psycho-spiritual changes, reportedly enabling improvements in personal orientation, priorities, and habits."

 

Link: https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-019-0333-3

Psychedelics Promote Structural and Functional Neural Plasticity

 

Published August 8th, 2018 by Calvin Ly et. al.

 

About: The authors of this study demonstrate that psychedelic compounds, like DMT and LSD, have the potential to promote neuroplasticity, specifically in the way that they increase dendritic arbor complexity, promote dendritic spine growth and stimulate synapse formation. 

 

Excerpt: "Because atrophy of cortical neurons is believed to be a contributing factor to the development of mood and anxiety disorders... we first treated cultured cortical neurons with psychedelics from a variety of structural classes... and measured the resulting changes in various morphological features... our results suggest that psychedelics may be used as lead structures to identify next-generation neurotherapeutics with improved efficacy and safety profiles."

 

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/

Research & Footnotes

The Pharmacology of Lysergic Acid Diethylamide: A Review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494066/

Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596041/

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591798/

Therapeutic Use of LSD in Psychiatry

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00943/full

LSD Therapy for Persons Suffering From Major Depression

https://clinicaltrials.gov/ct2/show/NCT03866252

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