Nor-LSD, or norLSD, also known as ''N'',''N''-diethyl-6-norlysergamide or as ''N''-desmethyllysergic acid diethylamide (''N''-desmethyl-LSD), is a serotonin receptor modulator and putative psychedelic of the lysergamide family related to

lysergic acid diethylamide Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a Semisynthesis, semisynthetic, Hallucinogen, hallucinogenic compound derived from ergot, known for its powerful psychological effects and ...

(LSD). It is the analogue of LSD in which the

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

at the 6 position of the ergoline

ring system A ring system is a disc or torus orbiting an astronomical object that is composed of solid material such as dust, meteoroids, planetoids, moonlets, or stellar objects. Ring systems are best known as planetary rings, common components of sate ...

has been removed.

Use and effects

According to

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

, nor-LSD showed no psychedelic effects at assessed doses of up to 500μg in humans, whereas LSD was active at doses as low as 50μg. Higher doses of nor-LSD do not appear to have been assessed.

Pharmacology

Pharmacodynamics

The drug showed 5- to 29-fold lower

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂ receptor compared to LSD (K_i = 30–158nM vs. 5.4nM, respectively). It also showed affinity for the serotonin 5-HT₁ receptor. In another more recent study however, nor-LSD showed similar or even higher affinities, activational potencies, and/or efficacies at the serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2B receptors as LSD, whereas it showed 36-fold lower affinity for the serotonin 5-HT_2C receptor compared to LSD. Nor-LSD failed to completely substitute for LSD in rodent drug discrimination tests even at very high doses. The greatest degree of substitution with nor-LSD was 75% at a dose of 7,420nM/kg, whereas 100% substitution occurred with LSD at a dose of 186nM/kg (a 40-fold lower dose). The was 2,594nM/kg for nor-LSD and 46nM/kg for LSD. Hence, nor-LSD was approximately 56-fold less potent than LSD in terms of producing LSD-like effects in rodents and failed to produce full LSD-like effects even at the highest assessed dose.

Pharmacokinetics

Nor-LSD has been reported to occur as a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of LSD in rats and humans.

Chemistry

Derivatives

Derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

s of nor-LSD substituted at the 6 position include LSD (METH-LAD; 6-methyl), ETH-LAD (6-ethyl), PRO-LAD (6-propyl), BU-LAD (6-butyl), AL-LAD (6-allyl), and PARGY-LAD (6-propynyl), among others. There appears to be a length of about 3carbon atoms that can be tolerated at the 6 position before potent psychedelic activity is lost.

History

Nor-LSD was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

, by Yuji Nakahara and Tetsukichi Niwaguchi, by at least 1971.

References

External links

Nor-LSD - Isomer Design
{{Ergolines 5-HT2A agonists 5-HT2B agonists Diethylamino compounds Enantiopure drugs Lysergic acid diethylamide Psychedelic lysergamides Serotonin receptor modulators