9,10-Dihydro-LSD

9,10-Dihydro-LSD, or 9,10-DH-LSD, also known simply as dihydro-LSD or as 9,10-dihydrolysergic acid diethylamide, is a non-hallucinogenic serotonin receptor modulator of the lysergamide family related to lysergic acid diethylamide. It is the analogue of LSD in which the 9,10- double bond in the D ring of the ergoline ring system has been hydrogenated.

Use and effects

In spite of its potent serotonin 5-HT_2A receptor agonism, 9,10-dihydro-LSD was found to be inactive in terms of psychedelic effects in humans. Whereas LSD is active at an oral dose of 1μg/kg, 9,10-dihydro-LSD was inactive orally at doses of up to 50μg/kg. As such, 9,10-dihydro-LSD does not produce psychedelic effects at doses of up to 50times the effective doses of LSD, demonstrating less than 2% of the potency of LSD in this regard.

Side effects

Despite lack psychedelic effects, 9,10-dihydro-LSD has nonetheless been reported to produce strong autonomic effects in humans, including nausea, emesis, tachycardia, shivering, polyuria, headache, and paresthesias, at doses of 100 to 200μg.

Pharmacology

Pharmacodynamics

The drug has been shown to bind to the serotonin 5-HT_2A, 5-HT_2C, and 5-HT_1A receptors. It acts as a partial agonist of the serotonin 5-HT_2A receptor similarly to LSD, whereas functional activities at the other serotonin receptors were not reported. At the serotonin 5-HT_2A receptor, 9,10-dihydro-LSD's affinity was 2.9nM, whereas its activational potency in terms of calcium release was 3,840nM and its intrinsic activity was 58%. Hence, 9,10-dihydro-LSD had about 2.7-fold lower affinity and 6-fold lower activational potency at the receptor compared to LSD, whereas its activational efficacy in terms of calcium release was about the same. At the serotonin 5-HT_2C and 5-HT_1A receptors, 9,10-dihydro-LSD showed 4.6-fold and 26-fold lower affinities than those of LSD, respectively. In earlier studies, 9,10-dihydro-LSD showed 52% of the serotonin antagonist activity of LSD in the isolated rat uterus in vitro.
It was reported to have failed to produce the autonomic or sympathomimetic effects typical of LSD and related psychedelics in animals, such as mydriasis, piloerection, and hyperthermia, although it did produce hypothermia.

Chemistry

Analogues

A number of analogues and derivatives of 9,10-dihydro-LSD are known, for instance dihydroergotoxine, a mixture of dihydroergocornine, dihydroergocristine, and dihydroergocryptine, and dihydroergotamine. Various 9,10-dihydrolysergamides are known to be very potent α-adrenergic antagonists, to have almost no effects on the uterus, and to have markedly reduced central effects. Dihydroergotoxine has been used to treat vascular disorders and essential hypertension, but has largely been discontinued. Other 9,10-Dihydrolysergamides have shown emetic activity. They often have comparable antiserotonergic activity relative to the saturated analogues. In general, 9,10-dihydrolysergamides are said to be devoid of hallucinogenic activity.

History

9,10-Dihydro-LSD was first described in the scientific literature by at least the 1950s.