LSD

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

Introduction

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. Studying ergot was what Hoffman at Sandoz was working on when he accidentally discovered the nervous properties of LSD.

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."

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... 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. At plasma 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 constituents of the plasma.

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 generating system. The new compound, 2-oxyLSD, does not possess LSD-like activity in the central nervous system.

Medical uses / Effects

Emerging Therapeutic Applications

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

More in Harm reduction

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)... 5, 10, and 20 μg LSD every fourth day over a 21-day period.

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.