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|Highs and lows|
You cannot say that LSD fries your brain because we've shown that if anything it makes your brain work better.
|—Interview with neuropsychopharmacologist David Nutt (52-insights.com)|
LSD, lysergic acid diethylamide, or LSD-25, is a semi-synthetic psychedelic drug that is derived from ergot alkaloids, which occur naturally in some plant diseases that infect rye, Achnatherum robustum ("sleepy grass") and other grains. The substance can bring about changes in the human nervous system in such small quantities that it was not, at first, believed possible (threshold dose is generally believed to be 20 micrograms, though there is some evidence of LSD affecting mood at even lower doses).
LSD was used extensively in psychiatric research in the 1960s, but society was afraid of anything that could blow Aldous Huxley's mind after Brave New World; so they enacted legal measures that made researching the beneficial effects of any hallucinogens extremely difficult. Medically, LSD has been shown to treat the pain symptoms of cluster headaches in low doses, and along with other psychedelic hallucinogens has shown some potential in treating alcoholism, nicotine addiction, and post-traumatic stress disorder in combination with standard psychotherapy (leading some to suspect that at least some 1960s users were self-medicating).
John Lilly experimented with giving LSD to dolphins to try to form computer terminal-assisted, linguistically-based inter-species communication. So far we haven't heard anything on how well it's worked.
How LSD works
At the basic level, what we know about LSD is that it is a serotonin agonist on various serotonin receptors subtypes — in other words, LSD basically binds to all the places serotonin would normally bind to, and changes how they act. The trippy psychedelic effects are thought to mostly be due to acid’s effect on the 5-HT2A receptor. Interestingly, LSD also has effects on dopamine and norepinephrine receptors — which most other psychedelics do not.
Effects on performance
In theory LSD should be a performance-reducing drug; however, in 1970 All-Star Pittsburgh Pirates pitcher Dock Ellis managed to deliver a no-hitter against the San Diego Padres under the influence of acid. Steve Jobs also claimed that Microsoft would be, all-in-all, a more interesting software company if Bill Gates had ever done acid. However, in a 1994 interview with Playboy magazine, Gates implied he had.[note 1]
Recent studies involving fMRI scans of the human brain on acid have shown that it not only doesn't reduce brain activity, but does quite the opposite — it creates a hyperconnected state of awareness in which axonal signalling is formed between cortices and lobes of the brain that otherwise never connect or interact with one another. The result is a human brain in which nearly all cortices are functioning at an extremely high rate of connectivity; in other words, if the intense world hypothesis is correct, this is in many ways artificially inducing an autistic state of mind. This state of overstimulated awareness can lead to potential fear and anxiety, especially if the user has pre-existing mental conditions, because all learned inhibition basically comes to the forefront of the conscious mind when using LSD. This means that repressed thoughts and memories become intensely vivid and inescapable — which has potential therapeutic use for obvious reasons, especially in the treatment of PTSD—  but in an uncontrolled environment, it can lead to a really bad damn trip.
Studies suggest that LSD might be somewhat effective in the treatment of Parkinson's disease- indeed, some of the prescription drugs that are prescribed by hospitals to treat Parkinson's are even modeled directly after LSD itself- for instance, Lisuride. Interestingly enough, a wide variety of drugs modeled from or pharmacologically similar[note 2] to LSD have often been used to treat a wide variety of physical illnesses, including (but not limited to) brain tumors, dementia, and strokes.
If you're a scientist like Francis Crick,[note 3] however, using LSD might lead to the discovery of something as revolutionary as DNA. (Side effects may include acquiring a taste for tinfoil haberdashery.) Or… if you're Kary Mullis,[note 4] LSD might help you (allegedly) invent PCR and kickstart a new era of biology research.
VICE: This study shows that acid sticks in people's serotonin receptors, maybe for days at a time. Can it stay in there forever and make people "permafried"?
David Nichols: It's pretty much a myth, [but] there are certain people who have a predisposition to certain types of mental illness — schizophrenia is the most commonly known one — those people will eventually develop schizophrenia. It hits you in your late teens and early 20s. So any kind of stressful event will cause the onset of that disorder. It's a developmental disorder, in the development of the cortex. So a lot of kids, they go off to college, and in that first semester, you're diagnosed with schizophrenia. Students [normally] have to go home because it's the stress, but they were primed for [schizophrenia]. Well, people who are primed for it, if they take a lot of LSD, it can trigger the onset of actual psychosis.
VICE: Yeah, but what if I take a really, really big dose?
David Nichols: In most circles, if you're mentally healthy, and you're not predisposed to psychosis, then you'll survive those big doses. I've talked to people who have taken massive doses of LSD, and they'll say, "I was high for a week, but then I came back. I thought I was going crazy, but then I came back." People who are not predisposed to mental illness basically survive those types of things. The people who are casualties are people who had a predisposition in the beginning. Probably any dose would have pushed them over the edge. That's sort of the current thinking.
When a trip goes bad, it can go bad. Feelings range from intense anxiety, paranoia, panic, terror, and/or feelings of insanity. Bad trips are more likely due to, or may be exacerbated by inexperience, improper preparation (hot tip: always bring water), poor environment, bad initial state of mind, or deeper issues such as depression or schizophrenia.
- Chemical Salvation? — A history of LSD, à la Jack Chick
- LSD Makes Your Brain More Like a Thesaurus: Scientists found the drug actually elevates an innate language ability. — Huffington Post (1 September 2016)
“”My errant youth ended a long time ago. […] That was on the other side of that boundary. The young mind can deal with certain kinds of gooping around that I don't think at this age I could. I don't think you're as capable of handling lack of sleep or whatever challenges you throw at your body as you get older. However, I never missed a day of work.
- In layman's terms, this means they target many of the same receptors, and have a similar effect on brain chemistry.
- Disclaimer: Francis Crick is an asshole who came up with his ideas based on stealing work of Rosalind Franklin, so he isn't exactly a great example.
- Also a lousy example because Mullis came down with a bad case of possibly acid-induced Nobel disease.
- Is It a Myth That LSD Can Permanently Fry Your Brain? Pharmacologist David Nichols told me that permanent acid trips make no medical sense. by Mike Pearl (February 5, 2017, 9:00pm) Vice.
- Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers by Anya K. Bershad et al. (2019) Biological Psychiatry 86(10):792-800. doi:10.1016/j.biopsych.2019.05.019.
- Dropping acid may help headaches: Cluster headache sufferers say LSD can abort attacks by Arran Frood (September 13th 2006) Nature.
- An LSD Trip Helped Me Quit Smoking by Thijs Roes (October 8, 2014, 7:00am) Vice.
- Reviewing the Potential of Psychedelics for the Treatment of PTSD by Erwin Krediet et al. (2020) International Journal of Neuropsychopharmacology' 23(6):385-400. doi:10.1093/ijnp/pyaa018.'
- Aghajanian, G. K., & Bing, O. H. (1964). Persistence of lysergic acid diethylamide in the plasma of human subjects. Clinical Pharmacology & Therapeutics, 5(5), 611-614. PMID: 14209776
- Moreno, J. L., Holloway, T., Albizu, L., Sealfon, S. C., & González-Maeso, J. (2011). Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience Letters, 493(3), 76-79. https://www.doi.org/10.1016/j.neulet.2011.01.046
- Marona-Lewicka, D., Thisted, R. A., & Nichols, D. E. (2005). Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis. Psychopharmacology, 180(3), 427-435. doi:10.1007/s00213-005-2183-9
- No Hitter
- "I wish him the best, I really do. I just think he and Microsoft are a bit narrow. He'd be a broader guy if he had dropped acid once or gone off to an ashram when he was younger." Steve Lohr. "Creating Jobs." The New York Times Magazine, 1997-01-12.
- The Bill Gates Interview: A candid conversation with the sultan of software about outsmarting his rivals (1994) Playboy.
- The Intense World Theory – A Unifying Theory of the Neurobiology of Autism by Kamila Markram & Henry Markram (2010) Front. Hum. Neurosci. 4:224. doi:10.3389/fnhum.2010.00224.
- Brain scans reveal how LSD affects consciousness: Drug researcher David Nutt discusses brain-imaging studies with hallucinogens by Zoe Cormier (11 April 2016) Nature.
- LSD-Assisted Psychotherapy: MAPS has completed the first double-blind, placebo-controlled study of the therapeutic use of LSD in human beings since the early 1970s. Multidisciplinary Association for Psychedelic Studies.
- See the Wikipedia article on Lisuride.
- See the Wikipedia article on Cabergoline.
- See the Wikipedia article on Ergoloid.
- The 5 Greatest Things Ever Accomplished While High by Jack O'Brien (August 04, 2008) Cracked.