Structure-Activity Studies on Tetrahydro- and Hexahydrocannabinol Derivatives

Skinner, W. A.; Rackur, Gerhard; Uyeno, Edward T.

doi:10.1002/jps.2600680319

Cited by 14 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Little attention has been paid to the pharmacological effects of HHCs, although some HHC derivatives were reported to have THC-like pharmacological effects [15][16][17]. In the present study, pharmacological effects of 9α-OH-HHC and 8-OH-iso-HHC have been assessed in mice by catalepsy, hypothermia, pentobarbital-induced sleep prolongation, and antinociception as indices, and have been compared with those of CBD or ∆ 9 -THC.…”

Section: Resultsmentioning

confidence: 97%

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

et al. 2007

View full text Add to dashboard Cite

sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED 50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respectively. The present study demonstrated that CBD can be converted to ∆ 9 -THC and its related cannabinoids, 9α-OH-HHC and 8-OH-iso-HHC, in artifi cial gastric juice, and that these HHCs show ∆ 9 -THC-like effects in mice, although their pharmacological effects were less potent than those of ∆ 9 -THC.

show abstract

Section: Resultsmentioning

confidence: 97%

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

et al. 2007

View full text Add to dashboard Cite

show abstract

“…When Δ 9 -THC is hydrogenated over palladium on charcoal catalyst, the ratios of the 9α-HHC and 9β-HHC isomers have been reported to be approximately 3:7 89 or 1:1. 95 Recently, a small-scale hydrogenation of an undefined isomeric mixture of Δ 8 /Δ 9 -THC using palladium on charcoal catalyst cartridge in a flow reactor has been reported. 96 It must be noted that heat-treatment of tetrahydrocannabinol derivatives in the presence of palladium on charcoal under non-reductive conditions results in aromatization furnishing CBN.…”

Section: Synthesis Of Hhc Based On Cannabidiol or Hemp Extractmentioning

confidence: 99%

Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review

Ujváry¹

2023

Drug Testing and Analysis

View full text Add to dashboard Cite

Since the early 2000s, there has been a turmoil on the global illicit cannabinoid market. Parallel to legislative changes in some jurisdictions regarding herbal cannabis, unregulated and cheap synthetic cannabinoids with astonishing structural diversity have emerged. Recently, semi‐synthetic cannabinoids manufactured from hemp extracts by simple chemical transformations have also appeared as recreational drugs. The burst of these semi‐synthetic cannabinoids into the market was sparked by legislative changes in the United States, where cultivation of industrial hemp restarted. By now, hemp‐derived cannabidiol (CBD), initially a blockbuster product on its own, became a “precursor” to semi‐synthetic cannabinoids such as hexahydrocannabinol (HHC), which appeared on the drug market in 2021. The synthesis and cannabimimetic activity of HHC were first reported eight decades ago in quest for the psychoactive principles of marijuana and hashish. Current large‐scale manufacture of HHC is based on hemp‐derived CBD extract, which is converted first by cyclization into a Δ8/Δ9‐THC mixture, followed by catalytic hydrogenation to afford a mixture of (9R)‐HHC and (9S)‐HHC epimers. Preclinical studies indicate that (9R)‐HHC has THC‐like pharmacological properties. The animal metabolism of HHC is partially clarified. The human pharmacology including metabolism of HHC is yet to be investigated, and (immuno)analytical methods for the rapid detection of HHC or its metabolites in urine are lacking. Herein, the legal background for the revitalization of hemp cultivation, and available information on the chemistry, analysis, and pharmacology of HHC and related analogs, including HHC acetate (HHC‐O) is reviewed.

show abstract

“…74 The 1-hydroxy group of Δ 9 -THC is essential for cannabinoid activity; conversion to a methyl ether (24) abolished activity, 71 as did removal, 75 whereas replacement of the C9 methyl group with an alcohol increased potency. 76 With respect to the 3pentyl chain, homologation, branching, and increased steric bulk all conferred improved potency, and the SAR of this region has been extensively reviewed. 64 Dimethylheptylpyran (DMHP, 25) was so potent that it was investigated as an incapacitating agent, EA-2233 (a racemic mixture of the O-acetyl esters of all 8 stereoisomers), during the Edgewood Arsenal experiments in the 1960s.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

“…The 1-hydroxy group of Δ 9 -THC is essential for cannabinoid activity; conversion to a methyl ether ( 24 ) abolished activity, as did removal, whereas replacement of the C9 methyl group with an alcohol increased potency . With respect to the 3-pentyl chain, homologation, branching, and increased steric bulk all conferred improved potency, and the SAR of this region has been extensively reviewed .…”

Section: Medicinal Chemistry Sar and Pharmacologymentioning

confidence: 99%

Dark Classics in Chemical Neuroscience: Δ⁹-Tetrahydrocannabinol

Banister

Arnold

Connor

et al. 2019

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally. The main psychoactive component of cannabis is (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), a compound with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ9-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB1) receptors. Δ9-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome. It is available as a regulated pharmaceutical in products such as Marinol, Sativex, and Namisol as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products. While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ9-THC itself. Robust contemporary debate surrounds the therapeutic value of Δ9-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug. This review will provide a profile of the chemistry, pharmacology, and therapeutic uses of Δ9-THC as well as the historical and societal import of this unique, distinctive, and ubiquitous psychoactive substance.

show abstract

Structure-Activity Studies on Tetrahydro- and Hexahydrocannabinol Derivatives

Cited by 14 publications

References 13 publications

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review

Dark Classics in Chemical Neuroscience: Δ⁹-Tetrahydrocannabinol

Contact Info

Product

Resources

About

Structure-Activity Studies on Tetrahydro- and Hexahydrocannabinol Derivatives

Cited by 14 publications

References 13 publications

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice

Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol

Contact Info

Product

Resources

About

Dark Classics in Chemical Neuroscience: Δ⁹-Tetrahydrocannabinol