LSD

LSD (lysergic acid diethylamide) was discovered in 1938 by Albert Hofmann at Sandoz Laboratories while researching ergot alkaloids. Its psychoactive properties were accidentally discovered in 1943, when Hofmann re-synthesized the compound and absorbed a trace through his skin.

LSD
Formula	C₂₀H₂₅N₃O
Type	Psychedelic / hallucinogen
Administration	Oral (sublingual, blotter), intravenous
Solubility	Water (as tartrate salt), ethanol; base form less water-soluble
Legal status	Schedule I (US), Class A (UK), Anlage I (Germany); controlled substance in most countries
Synonyms	LSD-25, lysergide, acid, "Lucy", trip
Bioavailability	~80% oral
Recommended dose	Standard dosages: 50-200 μg; threshold for psychotropic effects: ~10 μg
Upper limit
LD50	~46 mg/kg (IV, mice); ~16.5 mg/kg (IV, rats) - estimated from animal data. No confirmed human lethal dose exists; LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg)
Ray's verdict	Depends on context "A little bit of LSD by blocking the serotonin can open a person up... but the hallucinations are really not necessary for the positive effect of the drug to occur, they're just more of a side effect, a harmful side effect."

The bioenergetic perspective on LSD is considerably different from the mainstream narrative. The accumulating evidence for the first 15 or so years was very clear that LSD was a simple anti-serotonin action.

Ray Peat has noted:

LSD would block the serotonin-induced contraction of the uterus or of the blood vessel or of the intestine. Serotonin would block the kidney function so no urine was produced. LSD would restore kidney function. So since he saw straight across antagonism between LSD and serotonin, he proposed that the brain contains a small amount of serotonin and that LSD is having its effects by antagonizing this small amount of serotonin in the brain.

— Ray Peat

Dosing

Purpose	Dose Range
Microdose (sub-perceptual)	5-10 μg
Threshold / Consciousness expansion	10-20 μg
Standard psychoactive dose	50-200 μg
Strong dose	200-400 μg

Ray Peat's recommendation:

"The range of 10 to 20 micrograms is adequate for expanding consciousness."

"I think microdosing is on the level of 10 micrograms... but there are other more accessible ways to do the same thing - holding down uncontrolled production of serotonin, increasing its breakdown and preventing out-of-order production of serotonin."

Clinical Trial Dosing (Alzheimer's)

Volunteers were randomly assigned to 1 of 4 dose groups (5, 10, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days) over a 21-day period; no safety or cognitive-outcome abnormalities were found in any dose group.

Structure / Chemical properties

LSD is structurally related to the ergot alkaloids, which come from the fungus Claviceps purpurea. The ergot, a fungal disease of grains, was used for probably thousands of years to induce abortions; in the 19th century it was also tried to accelerate labor, but this was dangerous because it causes spasms not only in the uterus but in blood vessels.

The presence of considerable amounts of the drug in the brain and cerebrospinal fluid indicates that the substance can pass the blood-brain barrier. In guinea pig plasma at concentrations of 0.1 and 20 mg per liter, 90 and 65 per cent of LSD, respectively, was found to be bound to the nondiffusable (protein) constituents of the plasma; no equivalent human-plasma binding data exist.

Function / Mechanism of action

LSD's mechanism is complex and controversial. The mainstream view emphasizes 5-HT2A receptor agonism, while the bioenergetic perspective highlights its serotonin-antagonist properties.

The accumulating evidence for the first 15 or so years was very clear that LSD was a simple anti-serotonin action and that serotonin in overdose can make you crazy and hallucinate but it's a misery experience not an enlightenment experience.

These small amounts of LSD that will oppose serotonin on blood vessels and smooth muscles, all of the visible systems of the body, LSD is protective against serotonin and the stress experience. An unavoidable stress poisons you with serotonin, increases your tendency to be obedient, to want direction from the outside, and a little bit of LSD by blocking the serotonin can open a person up, get them out of this digitized world.

Tissue Distribution & Metabolism

LSD is almost completely metabolized in the body, only negligible amounts of the drug being excreted in the urine or the stools. The liver is the major site of metabolism of the drug.

LSD is transformed to 2-oxyLSD by an enzyme system present in liver microsomes that requires oxygen and a reduced-triphosphopyridine nucleotide (NADPH) generating system. The new compound, 2-oxyLSD, does not possess LSD-like activity in the central nervous system.

Medical uses / Effects

Emerging Therapeutic Applications

In a randomized trial of MM120 (lysergide d-tartrate), single doses of 50–100 μg produced rapid generalized-anxiety improvement lasting through 12 weeks; higher doses also reduced depression scores. LSD is now a potential ally. Neurodegenerative disease rates have skyrocketed, and the situation is especially dire with AD. In addition to rising rates of AD, death rates from AD have also skyrocketed, and since 2002 every single new drug tested on humans has failed.

The study describes the broad anti-inflammatory effects of LSD as one expected beneficial mechanism of action... LSD acts as an agonist on all known dopamine receptors.

Neuroprotective Effects

There's a new interest in LSD as a protective chemical. They're finding that it prevents nerve damage caused by some of the serotonergic excitotoxic chemicals. And they're even proposing it as an anti-psychotic treatment given in the right doses.

Effects on Consciousness

Peat offers an interesting perspective on LSD's cognitive effects:

I think the most important thing that the expanded consciousness does is to realize that consciousness extends through both time and space, that you're present in the oncoming future as well as the recent and more distant past. The digital civilization doesn't want people to experience themselves in that way.

The ability to dream in an awake state is an indication of high metabolic rate and that is a testament to serotonin's negative effect on metabolism, a serotonin antagonist like LSD intensifies greatly a biomarker (awake dreaming) of high metabolism.

Side / Adverse effects

Hallucinations as Overdose Effect

Ray Peat provides a counterintuitive perspective on hallucinogenic effects:

"I think some of the hallucination type experiences come from the overdose effect of LSD starting to act like ergot and serotonin and constricting blood vessels in the brain, shutting off energy production and leading to distortion of perception rather than opening and amplification."

"The hallucinations are really not necessary for the positive effect of the drug to occur. They're just more of a side effect - harmful side effect."

Other Adverse Effects

• Psychological disturbance ("bad trips"): particularly at higher doses
• Anxiety: more common with intravenous vs. oral administration
• Vasoconstriction: at higher doses, LSD begins acting more like ergot
• No physical dependence or addiction observed

Bad trips and emergency management

The peak effect of LSD occurs about 2 to 4 hours after ingestion, and effects can last up to 12 hours; monitored supervision is advised for at least the first 6 hours. Management is supportive: avoid stimulation and keep the person in a quiet room, de-escalate agitation, and monitor body temperature, with rehydration and external cooling if needed. Benzodiazepines are first-line for severe agitation, and serotonergic antiemetics such as ondansetron should be avoided. Cyproheptadine may be considered if serotonin syndrome is confirmed. Specific complications are hyperthermia and hyponatraemic cerebral oedema. Direct mortality is low, but deaths from behavior under the influence are documented. Haloperidol increased the psychosis-like effect of psilocybin in a human study, see Psilocybin. Call emergency services for high temperature, seizures, or confusion.

Brands and sources

Research/Clinical Settings:

• Originally produced by Sandoz Laboratories as "Delysid" (discontinued)
• Clinical-grade LSD tartrate is manufactured for approved research trials
• Companies like MindMed and Beckley Psytech are developing LSD formulations for clinical trials

Historical note: For the last 5+ decades, Big Pharma and public health officials together with the entire law enforcement apparatus have been propagating myths, lies and outright fraud in regards to psychedelic drugs and especially about LSD. This attitude grew out of the civil rights movement and protests in the 1960s.

Psilocybin

Psilocybin is the phosphorylated tryptamine in Psilocybe and related mushrooms; the body converts it to psilocin, which acts on serotonin pathways. In the bioenergetic frame it lines up with LSD as an anti-serotonin agent rather than a "happy serotonin" drug.

Dosing (Psilocybin)

Setting	Dose (as used in research)
Very-low / placebo-like comparator	1–3 mg / 70 kg
High dose (Griffiths cancer trial)	22–30 mg / 70 kg

Dried-mushroom milligram equivalents vary by species and potency; purified psilocybin doses above are from clinical protocols, not culinary "caps."

Structure / Chemical properties (Psilocybin)

Psilocybin is 4-phosphoryloxy-N,N-dimethyltryptamine. Alkaline phosphatase removes the phosphate to yield psilocin (4-hydroxy-DMT), the compound that crosses into the brain.

Function / Mechanism of action (Psilocybin)

Mainstream pharmacology emphasizes 5-HT2A agonism. Early anti-serotonin pharmacology of related tryptamines/LSD, and interview discussion of psilocybin, treat useful doses as suppressing serotonin nerve signaling the way LSD does.

Medical uses / Effects (Psilocybin)

Cancer-related depression and anxiety

In 51 patients with life-threatening cancer and depression and/or anxiety, a randomized double-blind cross-over compared a very-low psilocybin dose (1 or 3 mg/70 kg) with a high dose (22 or 30 mg/70 kg). High-dose sessions produced large drops in clinician- and self-rated depression and anxiety, with gains in quality of life and lower death anxiety; about 80% still showed clinically significant mood/anxiety improvement at 6 months.

Cluster headache

Interview and survey work on tryptamines notes cluster-headache relief with psilocybin/LSD in patients who used them.

Side / Adverse effects (Psilocybin)

• Psychoactive effects and possible anxiety or difficult sessions at full psychedelic doses
• High doses can include perceptual distortion; the useful anti-serotonin range may be below heavy hallucinogenic dosing (parallel to the LSD discussion)
• Legal and product-quality risks outside clinical supply

Harm reduction

Problem	Mechanism	Mitigation
Psychosis risk, more pronounced with high doses or frequent, repeated use	Serotonin-2A receptor agonism produces a psychosis-like syndrome in healthy volunteers that resembles first episodes of schizophrenia. It was blocked dose-dependently by the 5-HT2A antagonist ketanserin or the atypical antipsychotic risperidone, and increased by the dopamine antagonist haloperidol.	Avoid high doses and frequent, repeated use, and space sessions out. The useful anti-serotonin range may sit below heavy hallucinogenic dosing, see LSD.

Brands and sources (Psilocybin)

• Research/clinical psilocybin in regulated trials
• Wild or cultivated Psilocybe mushrooms (illegal in most jurisdictions; potency and contaminants vary)