An Introduction to LSD

PSYCHEDELICS

Nov 14

Liquid from a bottle is being poured into a syringe, showcasing a step in the injection preparation process. Photography: AI Generated by Grok.

What if there are doors your mind quietly keeps closed behind the everyday version of reality you've always trusted—doors that determine what's possible, what's meaningful, and what you're allowed to see?

Have you ever experienced a moment — while gazing at the sky, immersed in music, or simply daydreaming — when the usual filters faded away, and everything appeared strikingly vivid and meaningful, almost glowing with hidden patterns? And then, just as suddenly, the ordinary world returned to normal?

What if a single molecule — accidentally born in 1938 when a Swiss chemist was searching for something entirely different — could swing those doors wide open for 8–12 hours, letting light pour into corners of your mind you didn't even know were dark?

That molecule is LSD.

An introduction to LSD.

LSD (lysergic acid diethylamide, commonly pronounced "ell-ess-dee") is a potent synthetic psychedelic compound first synthesized in 1938 by Swiss chemist Albert Hofmann while researching ergot alkaloids. Often called "acid," it is one of the most potent psychoactive substances known, active in doses as small as 20–30 micrograms.

LSD is entirely human-made and does not occur in nature (though it is derived from ergot, a fungus that grows on rye). It gained fame in the 1940s and 1950s for psychiatric research and became a symbol of the 1960s counterculture. Today, it is most often encountered as blotter paper, microdots, or liquid.

Animated explainer: LSD's brain effects – 5-HT2A serotonin agonism, glutamate transmission, tolerance, non-addictive safety profile.

Chemistry & Molecular Structure.

LSD (lysergic acid diethylamide) is a semisynthetic ergoline alkaloid derived from lysergic acid, a natural compound found in the ergot fungus (Claviceps purpurea) that grows on rye and other grains. Chemically, LSD belongs to the ergoline and tryptamine families and is structurally closely related to serotonin (5-HT), which explains its powerful action on serotonin receptors—especially the 5-HT₂A receptor.

Unlike psilocybin, LSD is not metabolized into other active compounds after ingestion and retains its potency as it crosses the blood-brain barrier. Its strong affinity for the 5-HT₂A receptor (Ki ≈ 1–3 nM) makes it one of the most potent psychoactive substances, with doses measured in micrograms.

Skeletal formula of LSD (lysergic acid diethylamide) molecule – chemical structure of acid, the potent 5-HT2A agonist used in therapy and microdosing. Photography: Wikimedia

History and cultural significance.

Ancient Use: Thousands of Years Before the Term "Psychedelics" Existed:

Unlike psilocybin, LSD has no documented ancient use, as it is a fully synthetic compound created in the 20th century.

The Most Famous Modern Rediscovery: Albert Hofmann (1943):

1938: Swiss chemist Albert Hofmann first synthesized LSD (lysergic acid diethylamide) at Sandoz Laboratories in Basel while researching ergot derivatives for circulatory stimulants.
1943: On April 16, Hofmann accidentally absorbed a trace amount during resynthesis, experiencing mild hallucinations; three days later, he intentionally ingested 250 µg, embarking on the world's first deliberate LSD trip—now celebrated as "Bicycle Day" after his ride home.

Western Science Enters the Picture:

From 1947–1966, Sandoz distributed LSD (as Delysid) to over 2,000 researchers worldwide for psychiatric studies, showing promise in treating alcoholism, anxiety, and schizophrenia—over 1,000 papers documented its use in psychotherapy.
In the early 1950s, the CIA's MKUltra program (1953–1973) secretly tested LSD on unwitting subjects, including prisoners and civilians, for mind control and interrogation, dosing over 7,000 people and contributing to tragedies like the 1953 death of scientist Frank Olson.

The 1960s Boom and the Backlash:

From 1959 to 1963, Harvard's Timothy Leary and Richard Alpert (later Ram Dass) led the Harvard Psilocybin Project, but shifted to LSD, experimenting on students and prisoners; Leary's mantra "turn on, tune in, drop out" popularized it as a tool for spiritual awakening and anti-establishment rebellion.
LSD fueled the counterculture: Ken Kesey's Acid Tests, the Grateful Dead, and events like the 1967 Human Be-In drew millions, but media-fueled "LSD panic" over bad trips and chromosome damage (later debunked) led to the 1966 U.S. ban; Leary was ousted from Harvard in 1963.
The project was shut down amid controversy, and LSD was classified as a Schedule I substance in the U.S. under the Controlled Substances Act of 1970.

50 Years in the Shadows (1970–2000):

Almost all human research halted after the 1971 UN Convention on Psychotropic Substances, which placed LSD in Schedule I globally, prohibiting non-research use; U.S. funding dried up, and stigma from counterculture associations buried therapeutic potential.

The Modern Renaissance (2000–2025):

In 2014, the first modern LSD-assisted psychotherapy trial at the University of Basel (Gasser et al.) showed reduced anxiety in terminal cancer patients; by 2025, over 20 trials explored LSD for depression, addiction, and cluster headaches.
In 2020, Oregon's Measure 109 legalized supervised psilocybin, inspiring LSD efforts; by 2025, Washington D.C. and cities like Tacoma, WA, decriminalized natural psychedelics, with bills in California and Massachusetts eyeing LSD inclusion for veterans' PTSD treatment.
In March 2024, the FDA granted breakthrough therapy status to MM-120 (LSD derivative) for anxiety, fast-tracking trials; Phase 3 studies for depression and GAD are underway.

Cultural Significance Today:

Books like Michael Pollan's How to Change Your Mind (2018) and its 2022 Netflix series have mainstreamed LSD's history and potential, reaching millions; documentaries such as The Sunshine Makers (2015) and LSD: The Beyond Within (2020) highlight its countercultural legacy.

Netflix trailer: How to Change Your Mind docuseries on LSD, psilocybin, MDMA, mescaline – Michael Pollan explores psychedelic healing.

Podcasts by Tim Ferriss, Joe Rogan, and Aubrey Marcus feature LSD researchers, normalizing discussions; by 2025, LSD is no longer fringe—it's in therapy trials, art exhibits, and policy debates. Thoughtful voices emphasize ethical sourcing and integration, honoring its synthetic origins while addressing past abuses like MKUltra. This foundation guides responsible use in a world grappling with mental health crises.

Joe Rogan podcast clip: Rick Doblin on MDMA therapy for PTSD, MAPS trials, psychedelic healing & 2025 science conference.

How LSD works in the brain, common effects, and experiences.

Time After Ingestion: 0-30 Minutes (Come up).

What Happens in the Body and Brain: LSD absorption and initial 5-HT₂A receptor binding.
Detailed Neurological Explanation: LSD is rapidly absorbed from the gastrointestinal tract into the bloodstream, peaking in 1.4–1.5 hours, and begins affecting the brain by binding to serotonin 5-HT₂A receptors.
What You Might Notice: You may experience slight nausea or jitteriness from the "body load," along with subtle mood shifts, yawning, pupil dilation, and a building sense of anticipation or mild anxiety.

Time After Ingestion: 30-90 Minutes (Peak Onset).

What Happens in the Body and Brain: Rising 5-HT₂A receptor activation. The Default Mode Network (DMN) begins to ↓. Brain entropy starts to ↑.
Detailed Neurological Explanation: LSD's direct agonism at 5-HT₂A receptors quiets the DMN (involved in self-referential thinking), increases global brain connectivity, and boosts neural signal complexity (entropy), fostering novel associations across sensory and cognitive networks.
What You Might Notice: The "whoa" moment: open-eye visuals emerge (tracers, enhanced colors), time feels elastic, emotions intensify, and a sense of wonder or unease builds. Peak intensity ramps up toward 60–90 minutes.

Time After Ingestion: 90 Minutes-2 Hours (Deep Immersion).

What Happens in the Body and Brain: Maximum 5-HT₂A-driven network reconfiguration.
Detailed Neurological Explanation: Thalamic filtering relaxes, flooding sensory input; hyperconnectivity forms between segregated regions (e.g., visual cortex and emotional hubs), while DMN desynchronization promotes ego loosening and cross-modal perceptions.
What You Might Notice: Profound visuals (geometric patterns, fractals), synesthesia (sounds as colors), mystical insights, or complete ego dissolution—profound unity or boundary loss.

Time After Ingestion: 2-4 Hours (Plateau/Descent).

What Happens in the Body and Brain: Sustained cross-talk, as plasma levels peak and begin a gradual decline.
Detailed Neurological Explanation: LSD peaks at ~1.3–3.1 ng/mL; metabolism starts, but introspection continues with reduced intensity.
What You Might Notice: The height eases into reflective waves—deep emotional releases, philosophical reveries, laughter, or tears. You gain more "control," navigating insights with less overwhelm.

Time After Ingestion: 4-6 Hours (Return & Reflection Phase).

What Happens in the Body and Brain: Effects wane as LSD clears.
Detailed Neurological Explanation: Plasma levels fall below 5-HT₂A activation thresholds (~2.6–3.7 hours half-life), enabling partial reintegration of DMN and baseline hierarchies, though residual entropy remains.
What You Might Notice: "Afterglow" sparks—euphoria, clarity, or light fatigue emerge. Visuals soften into mild tracers, and you feel increasingly grounded as you process the journey.

Time After Ingestion: 6-24 Hours (Afterglow).

What Happens in the Body and Brain: Acute afterglow & early neuroplastic window.
Detailed Neurological Explanation: BDNF levels peak around 6 hours, enhancing synaptic strengthening and dendritic growth, allowing brief rewiring through increased TrkB signaling.
What You Might Notice: Classic afterglow: uplifted mood, vivid colors in daily life, gratitude, and subtle perceptual shifts. Sleep may be vivid or restorative.

Time After Ingestion: Days to Months later (Integration Period).

What Happens in the Body and Brain: Lasting neuroplasticity.
Detailed Neurological Explanation: Sustained BDNF/TrkB effects boost dendritic spine density and DMN flexibility in responders, fostering long-term circuit adaptations without permanent structural overhaul.
What You Might Notice: Enduring mood lifts, greater openness, cognitive agility, and perspective shifts—often described as "personally meaningful" changes lasting weeks to months.

Potential benefits and therapeutic uses of LSD.

Clinical trials now show LSD-assisted therapy (typically 1–2 guided sessions with 100–200 µg doses) can produce rapid, lasting relief for:

Treatment-resistant and major depression (50–60% remission rates lasting 6–12+ months, often with sustained antidepressant effects outperforming traditional SSRIs in early Phase II/III data).
End-of-life anxiety in cancer patients (single dose → 77% sustained reductions in anxiety lasting up to 12 months).
Addiction (strong historical results for alcohol use disorder with 50–60% abstinence rates at 6–12 months; emerging data for opioids and tobacco, with ongoing trials showing promise).
Early promise for PTSD, OCD, and cluster headaches (observational studies report reduced symptoms in trauma-related disorders; Phase III trials underway for generalized anxiety, with potential extensions to PTSD).

Healthy volunteers often report greater openness, life satisfaction, and a lasting connection to others and nature. The combination of a profound personal experience and a "reset" of stagnant brain networks explains why the benefits are often so enduring.

Risks, side effects, and safety concerns while using LSD.

LSD is one of the safest psychoactive substances regarding physical toxicity. There have been no confirmed overdose deaths from LSD alone; it has an extremely low potential for addiction, and its lethal dose is estimated to be thousands of times greater than a typical recreational amount (e.g., LD50 >14,000 µg vs. 100–200 µg dose).

Common Acute Side Effects (usually resolve within hours):

Nausea and vomiting are very common, especially during the come-up, along with dry mouth and loss of appetite.
Headaches, dizziness, and transiently elevated blood pressure and heart rate can also occur, driven by sympathomimetic effects.
Additionally, feelings of anxiety, paranoia, or confusion may arise during the experience, often tied to the "body load."

Psychological Risks:

Challenging experiences during trips can involve intense fear, paranoia, or temporary psychosis-like states. These risks are most common with unsupervised use and are rare in guided settings.
Additionally, such experiences can trigger or worsen mental health issues in individuals with a personal or family history of schizophrenia, bipolar disorder, or severe anxiety. Strict screening processes are used to exclude these individuals in clinical trials.
There have also been rare cases of increased thoughts of suicide or suicidal behavior following sessions, particularly observed in some depression trials or bad trips.

Rare Long-Term Concerns:

Hallucinogen Persisting Perception Disorder (HPPD) involves visual "flashbacks" or disturbances, such as snow, trails, and halos, lasting from weeks to years. It affects fewer than 5% of users and is often mild or benign.
Flashbacks, brief re-experiencing episodes, are common but typically not distressing, occurring in 9–25% of users post-trip.

Other Important Safety Issues:

Adulteration risks → Accidental ingestion of toxic mimics like NBOMe compounds sold as "acid" (seizures, heart failure possible).
Mixing with other substances (alcohol, stimulants, antidepressants) → Increases risk of bad trips, paranoia, or serotonin syndrome (e.g., with SSRIs or MAOIs).
Cardiovascular strain → Caution if pre-existing heart conditions, due to potential for hypertension or arrhythmias.
Legal risks → Still Schedule I federally in the U.S. (illegal outside research contexts; possession can lead to felony charges).

Key Takeaway:

In controlled clinical settings that include screening, preparation, and support, serious adverse events related to LSD are rare, and there have been no reported deaths attributed to its use. However, unsupervised recreational use poses greater psychological risks, particularly for vulnerable individuals.

Dosage, Preparation, Set & Setting.

LSD dosages are measured in micrograms (µg) and are commonly available in forms such as blotter paper, liquid, or microdots. Its high potency enables precise microgram-level dosing, often verified by volumetric methods using distilled water or alcohol.

Common dosage categories are as follows:

Microdose: 5–20 µg (sub-perceptual effects like subtle mood enhancement or focus without hallucinations).
Low/Threshold dose: 25–75 µg (mild perceptual shifts, enhanced colors, and emotional openness without full immersion).
Moderate/Therapeutic dose: 75–150 µg (classic trip with visuals, introspection, and ego softening; standard for therapy trials).
High/Heroic dose: 200–400+ µg (intense ego dissolution, profound insights, and synesthesia; reserved for experienced users).

These classifications help users understand the effects and purposes of different dosages, noting that tolerance builds rapidly and resets in 3 to 4 days.

Preparation is crucial for a positive experience. Fasting for 3 to 4 hours or having a light meal can help prevent nausea. LSD does not require a "lemon tek," as it is already active. Instead, you can achieve accurate dosing by dissolving a tab in 10 mL of distilled water (1 mL = about 10% of a 100 µg tab) and consider sublingual placement for faster effects. Having water and light snacks available, and allowing 12 to 24 hours of calm afterward for integration, is recommended.

Set and setting are vital safety factors that significantly influence the experience's outcome.

Approaching the experience with clear intention and emotional stability, without acute life crises. Individuals with a personal or family history of schizophrenia, bipolar disorder, or severe anxiety are generally advised to avoid LSD.

The setting refers to the physical and social environment in which an experience takes place. An ideal setting is a quiet, comfortable, and familiar space, equipped with soft lighting, blankets, and a carefully selected music playlist.

For doses exceeding 75 µg, it is highly recommended to have a trusted, sober sitter or guide present. Clinical trials indicate that proper psychological support significantly reduces the likelihood of challenging experiences, decreasing the rate from approximately 30% (without supervision) to under 5%.

Myths and Misconceptions.

"It's highly addictive." False. LSD has one of the lowest abuse potentials of any psychoactive substance; no physical dependence, almost no cravings, and tolerance develops rapidly, discouraging repeated use.

"You can overdose and die." Practically impossible. The lethal dose is thousands of times higher than a strong recreational dose; there have been no confirmed deaths from LSD alone.
"It causes permanent insanity." Extensive population studies and modern trials show no link in healthy, screened people. Risk exists only for those with a history of schizophrenia or bipolar disorder.
"It fries your brain." The opposite: it promotes new brain connections and plasticity, enhancing neural connectivity without long-term damage.
"Flashbacks/HPPD are common and terrifying." They affect <5 % of users and are usually mild and temporary, often resolving without intervention.

Most fears come from 1960s propaganda, not evidence.

How to Test LSD (Harm Reduction Guide).

The gold standard for beginners is a multi-reagent kit with at least Ehrlich and Hofmann. These two together positively identify LSD and rule out the most common dangerous adulterants like NBOMes or DOx compounds.

I get my test kits from this Norwegian website.

Basic How-To Use (Safe & Simple):

Scrape a tiny sample (match-head size, ~10–20 mg) from your blotter, liquid, or microdot onto a clean ceramic plate or test vial. Use separate spots for each reagent. For liquid LSD, let a drop dry on plain paper first.
Add 1–2 drops of reagent.
Watch the color change immediately (within 5–60 seconds, though Hofmann may take up to 30 minutes). Compare to the chart included or online.
Dispose safely (reagents are corrosive).

Expected Reactions for Pure LSD:

Ehrlich: Turns purple (bright violet/pink; confirms the presence of indoles like LSD).
Hofmann: Deep blue (distinguishes lysergamides like LSD from other indoles, which turn yellow-green).

Red Flags - Do NOT consume:

No color change or wrong color (e.g., no purple with Ehrlich = no LSD/indole; yellow/green with Hofmann = non-lysergamide).
Faint or delayed reaction = possible low dose or analog like 1P-LSD (test further).
Add Marquis/Mecke if suspicious: No black/purple = likely amphetamine or nothing.

Advanced Option – Purity/Quantitative Testing:

Reagents can only confirm the presence of a substance, not its purity. To estimate the purity percentage or microgram dosage, you can use a colorimetric QTest such as the Miraculix LSD QTest.

For this test, dissolve a sample and compare the resulting color to the provided scale.

For a more accurate analysis, consider mailing a sample to Energy Control in Spain or DrugsData.org in the USA. This service is anonymous and costs approximately $100-$150.

Key Takeaway:

Testing takes five minutes and can save your life. No reaction = safe is a myth—always use multiple reagents. When in doubt, throw it out. Harm reduction saves lives!

LSD testing demo: Ehrlich (purple) & Hofmann (blue) reagents on blotter paper for purity confirmation & harm reduction.