Delta-8 Tetrahydrocannabinol Product Impurities

Ray, Colleen L.; Bylo, Madison P.; Pescaglia, Jonny; Gawenis, James A.; Greenlief, C. Michael

doi:10.3390/molecules27206924

Cited by 14 publications

(9 citation statements)

References 5 publications

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“…149,150 Additional impurities may originate from plant-derived minor cannabinoids, such as cannabidivarin, cannabidihexol, or tetrahydrocannabihexol, carried over from the hemp plant during extraction. 135,151 Interestingly, some analytical certificates posted on the Internet for HHC products reported non-hydrogenated cannabinoids, such as CBD, CBG, and CBGA as minor components. 152 HHC is often sold in vaping products.…”

Section: Potential Contaminants In Hhc Preparationsmentioning

confidence: 99%

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

Ujváry¹

2023

Drug Testing and Analysis

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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.

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Section: Potential Contaminants In Hhc Preparationsmentioning

confidence: 99%

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

Ujváry¹

2023

Drug Testing and Analysis

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“…Ray et al (2022) used 1 H-NMR, HPLC-UV, and HPLC-MS to determine unknown impurities in Δ 8 -THC consumer products purchased online or from local retailers from the USA [ 66 ]. Ten Δ 8 -THC products, including distillates and vaporizers, were analyzed during the study.…”

Section: Analysis Of δ 8 -Thcmentioning

confidence: 99%

“…The identified compounds included cannabidivarin (CBDV) and cannabidihexol (CBDH). The study concluded that the problem with these products is threefold: impure CBD starting material, poor post-reaction purification, and inadequate separation of closely related cannabinoids during laboratory analysis of the final product [ 66 ].…”

Section: Analysis Of δ 8 -Thcmentioning

confidence: 99%

Chemistry and Pharmacology of Delta-8-Tetrahydrocannabinol

Abdel-Kader,

Radwan,

Metwaly

et al. 2024

Molecules

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Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern hemisphere, its use has moved and flourished in the Western nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis, with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. The passing of the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents, as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

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“…Because the methods used to convert CBD to Δ 8 -THC are not specifically addressed in hemp laws, the legality of synthetic Δ 8 -THC stays unclear. This raises safety and product quality concerns for consumers given the unknown and untested nature of Δ 8 -THC, other synthetic analogs, and any other impurities present 24 , 25 , 26 .…”

Section: Introductionmentioning

confidence: 99%

“…Because the methods used to convert CBD to Δ 8 -THC are not specifically addressed in hemp laws, the legality of synthetic Δ 8 -THC stays unclear. This raises safety and product quality concerns for consum-ABBREVIATIONS 4,8-epoxy-iso-THC 4,8-epoxy-iso-tetrahydrocannabinol 8-OH-iso-THC United States Pharmacopeia Δ 4,8 -iso-THC Δ 4,8 -iso-tetrahydrocannabinol Δ 4 -iso-THC Δ 4 -iso-tetrahydrocannabinol Δ 8 -cis-iso-THC Δ 8 -cis-iso-tetrahydrocannabinol Δ 8 -iso-THC Δ 8 -iso-tetrahydrocannabinol Δ 8 -THC trans-Δ 8 -tetrahydrocannabinol Δ 9 -THC trans-Δ 9 -tetrahydrocannabinol ers given the unknown and untested nature of Δ 8 -THC, other synthetic analogs, and any other impurities present [24][25][26]. U. S. health officials are warning about the potential dangers of Δ 8 -THC following hospitalizations tied to the substance.…”

mentioning

confidence: 99%

Development and Validation of a GC-FID Method for the Quantitation of Δ 8-Tetrahydrocannabinol and Impurities Found in Synthetic Δ 8-Tetrahydrocannabinol and Vaping Products

Gul,

Shahzadi,

Sarma

et al. 2024

Planta Med

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Concerns about health hazards associated with the consumption of trans-delta-8-tetrahydrocannabinol products were highlighted in public health advisories from the U. S. Food and Drug Administration and U. S. Centers for Disease Control and Prevention. Simple and rapid quantitative methods to determine trans-delta-8-tetrahydrocannabinol impurities are vital to analyze such products. In this study, a gas chromatography-flame ionization detection method was developed and validated for the determination of delta-8-tetrahydrocannabinol and some of its impurities (recently published) found in synthesized trans-delta-8-tetrahydrocannabinol raw material and included olivetol, cannabicitran, Δ 8-cis-iso-tetrahydrocannabinol, Δ 4-iso-tetrahydrocannabinol, iso-tetrahydrocannabifuran, cannabidiol, Δ 4,8-iso-tetrahydrocannabinol, Δ 8-iso-tetrahydrocannabinol, 4,8-epoxy-iso-tetrahydrocannabinol, trans-Δ 9-tetrahydrocannabinol, 8-hydroxy-iso-THC, 9α-hydroxyhexahydrocannabinol, and 9β-hydroxyhexahydrocannabinol. Validation of the method was assessed according to the International Council for Harmonization guidelines and confirmed linearity with R2 ≥ 0.99 for all the target analytes. The limit of detection and limit of quantitation were 1.5 and 5 µg/mL, respectively, except for olivetol, which had a limit of detection of 3 µg/mL and a limit of quantitation of 10 µg/mL. Method precision was calculated as % relative standard deviation and the values were less than 8.4 and 9.9% for the intraday precision and inter-day precision, respectively. The accuracy ranged from 85 to 118%. The method was then applied to the analysis of 21 commercially marketed vaping products claiming to contain delta-8-tetrahydrocannabinol. The products analyzed by this method have various levels of these impurities, with all products far exceeding the 0.3% of trans-Δ 9-tetrahydrocannabinol limit for hemp under the Agriculture Improvement Act of 2018. The developed gas chromatography-flame ionization detection method can be an important tool for monitoring delta-8-tetrahydrocannabinol impurities in commercial products.

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Delta-8 Tetrahydrocannabinol Product Impurities

Cited by 14 publications

References 5 publications

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

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

Chemistry and Pharmacology of Delta-8-Tetrahydrocannabinol

Development and Validation of a GC-FID Method for the Quantitation of Δ 8-Tetrahydrocannabinol and Impurities Found in Synthetic Δ 8-Tetrahydrocannabinol and Vaping Products

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