8,9-Dihydrocannabidiol

Last updated
8,9-Dihydrocannabidiol
New H2CBD.png
Names
Preferred IUPAC name
2-[(1S,6S)-3-Methyl-6-(propan-2-yl)cyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol
Other names
H2CBD, DiHydroCBD
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C21H32O2/c1-5-6-7-8-16-12-19(22)21(20(23)13-16)18-11-15(4)9-10-17(18)14(2)3/h11-14,17-18,22-23H,5-10H2,1-4H3/t17-,18+/m0/s1
    Key: PCXRACLQFPRCBB-ZWKOTPCHSA-N
  • CCCCCC1=CC(=C(C(=C1)O)[C@@H]2C=C(CC[C@H]2C(C)C)C)O
Properties
C21H32O2
Molar mass 316.485 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

8,9-Dihydrocannabidiol (also known as H2CBD, DiHydroCBD, Delta-1-H2CBD, or Delta-1-DiHydroCBD) is a synthetic cannabinoid that is closely related to cannabidiol (CBD) itself. [1] [2] that was first synthesized by Alexander R. Todd in 1940 derived from the catalytic hydrogenation of cannabidiol. [3]

Contents

Pharmacology

It may have certain advantages over CBD, in that it is fully synthetic, inexpensive to produce, and it is not a scheduled drug (cannabis extracts are controlled substances in most parts of the world). In addition, there is no path to synthesize the psychoactive substance tetrahydrocannabinol (THC) from H2CBD. CBD has been shown to convert to some extent to THC in the gastric tract, [4] [5] and the deliberate laboratory conversion of CBD to THC is straightforward. [6] [7] H2CBD has therefore been studied for its potential use as an alternative to CBD in terms of its lack of abuse liability and absence of psychotropic effects. [1] [8] [9]

It was shown to have anti-seizure activity essentially identical to that of CBD in tests with rats. [10]

In 2006 it was reported that 8,9-Dihydrocannabidiol binds very weakly to the CB1 receptor with a binding affinity higher than 1μM but was noted to have potential anti-inflammatory effects independent of its cannabinoid receptor action. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Tetrahydrocannabinol</span> Psychoactive component of cannabis

Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis. It is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term THC usually refers to the delta-9-THC isomer with chemical name (−)-trans-Δ9-tetrahydrocannabinol. It is a colorless oil.

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 100 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<span class="mw-page-title-main">Cannabinol</span> Naturally-occurring cannabinoid

Cannabinol (CBN) is a mildly psychoactive phytocannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

<span class="mw-page-title-main">Cannabidiol</span> Phytocannabinoid discovered in 1940

Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple forms of epilepsy. It was discovered in 1940 and, as of 2024 clinical research on CBD included studies related to the treatment of anxiety, addiction, psychosis, movement disorders, and pain, but there is insufficient high-quality evidence that CBD is effective for these conditions. CBD is sold as an herbal dietary supplement and promoted with yet unproven claims of particular therapeutic effects.

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes. THCV was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">Tetrahydrocannabutol</span> Chemical compound

Δ9-Tetrahydrocannabutol is a phytocannabinoid found in cannabis that is a homologue of tetrahydrocannabinol (THC), the main active component of Cannabis. Structurally, they are only different by the pentyl side chain being replaced by a butyl side chain. THCB was studied by Roger Adams as early as 1942

<span class="mw-page-title-main">Cannabichromene</span> Chemical compound

Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, exhibits anti-inflammatory properties in vitro, which may, theoretically, contribute to cannabis analgesic effects. It is a phytocannabinoid, one of the hundreds of cannabinoids found in the Cannabis plant. It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabinol (CBN), among others. CBC and cannabinols are present in cannabis. It is not scheduled by the Convention on Psychotropic Substances.

<span class="mw-page-title-main">Dronabinol</span> Generic name of Δ9-THC in medicine

Dronabinol, sold under the brand names Marinol and Syndros, is the generic name for the molecule of (−)-trans-Δ9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant, antiemetic, and sleep apnea reliever and is approved by the U.S. Food and Drug Administration (FDA) as safe and effective for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting.

<span class="mw-page-title-main">CBD-DMH</span> Chemical compound with cannabinoid effects

Cannabidiol-dimethylheptyl (CBD-DMH or DMH-CBD) is a synthetic homologue of cannabidiol where the pentyl chain has been replaced by a dimethylheptyl chain. Several isomers of this compound are known. The most commonly used isomer in research is (−)-CBD-DMH, which has the same stereochemistry as natural cannabidiol, and a 1,1-dimethylheptyl side chain. This compound is not psychoactive and acts primarily as an anandamide reuptake inhibitor, but is more potent than cannabidiol as an anticonvulsant and has around the same potency as an antiinflammatory. Unexpectedly the “unnatural” enantiomer (+)-CBD-DMH, which has reversed stereochemistry from cannabidiol, was found to be a directly acting cannabinoid receptor agonist with a Ki of 17.4nM at CB1 and 211nM at CB2, and produces typical cannabinoid effects in animal studies, as does its 7-OH derivative.

<span class="mw-page-title-main">Tetrahydrocannabiphorol</span> Cannabinoid agonist compound

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB1 and CB2 receptor agonist which was known as a synthetic homologue of tetrahydrocannabinol (THC), but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa.

<span class="mw-page-title-main">7-Hydroxycannabidiol</span> Chemical compound

7-Hydroxycannabidiol (7-OH-CBD) is an active metabolite of cannabidiol, generated in the body from cannabidiol by the action of the enzyme CYP2C19. While methods have been developed for its synthetic production, and measurement of levels in the body following consumption of cannabidiol, its pharmacology has been relatively little studied, though it has been found to possess similar anticonvulsant effects to cannabidiol itself, as well as lowering blood triglyceride levels. Like its precursor CBD, it is not known to exhibit any psychoactive effects on the body and is known to counter the psychoactive effects of THC if it is present at the same time. This mode of action in 2015 was discovered to be at least contributing in part by being a non competitive negative allosteric modulator of the Cannabinoid receptor type 1.

<span class="mw-page-title-main">Δ-10-Tetrahydrocannabinol</span> Isomer of tetrahydrocannabinol

Δ-10-Tetrahydrocannabinol is a positional isomer of tetrahydrocannabinol, discovered in the 1980s. Two epimers have been reported in the literature, with the 9-methyl group in either the (R) or (S) conformation; of these, the (R) epimer appears to be the more active isomer as well as the double bond in the 10th position instead of the 9th maintaining about 30 to 40 percent the potency of delta-9-THC. Δ10-THC has rarely been reported as a trace component of natural cannabis, though it is thought to be a degradation product similar to cannabinol rather than being produced by the plant directly. However, it is found more commonly as an impurity in synthetic delta-8-THC produced from cannabidiol and can also be synthesized directly from delta-9-THC.

<span class="mw-page-title-main">Hexahydrocannabinol</span> Hydrogenated derivative of THC

Hexahydrocannabinol (HHC) is a hydrogenated derivative of tetrahydrocannabinol (THC). It is a naturally occurring phytocannabinoid that has rarely been identified as a trace component in Cannabis sativa, but can also be produced synthetically by firstly acid cyclization of cannabidiol and then hydrogenation of tetrahydrocannabinol. The synthesis and bioactivity of HHC was first reported in 1940 by Roger Adams.

<span class="mw-page-title-main">11-Hydroxyhexahydrocannabinol</span> Chemical compound

11-Hydroxyhexahydrocannabinol is an active metabolite of tetrahydrocannabinol (THC) and a metabolite of the trace cannabinoid hexahydrocannabinol (HHC).

<span class="mw-page-title-main">7,8-Dihydrocannabinol</span> Chemical compound

7,8-Dihydrocannabinol (7,8-DHC) is a trace component of cannabis. Despite its structural similarity to active cannabinoids such as tetrahydrocannabinol and cannabinol, its pharmacology has not been studied.

Cannabinoids are compounds found in the cannabis plant or synthetic compounds that can interact with the endocannabinoid system. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (Delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is another major constituent of some cannabis plants. Conversion of CBD to THC can occur when CBD is heated to temperatures between 250–300 °C, potentially leading to its partial transformation into THC.

<span class="mw-page-title-main">H4-CBD</span> Chemical compound

H4CBD is a cannabinoid that was first synthesized by Alexander R. Todd in 1940 derived from the catalytic hydrogenation of cannabidiol.

<span class="mw-page-title-main">H2-CBD</span> Chemical compound

H2CBD are cannabinoids that were first synthesized by Alexander R. Todd in 1940 by catalytic hydrogenation of cannabidiol.

<span class="mw-page-title-main">Cannabidiol diacetate</span> Chemical compound

Cannabidiol diacetate is a semi-synthetic derivative of cannabidiol derived by acetylation of the OH groups, which presumably acts as a prodrug for CBD. It has been found as a component of grey-market cannabis products such as e-cigarette liquids and edible gummy lollies.

Conversion of cannabidiol (CBD) to tetrahydrocannabinol (THC) can occur through a ring-closing reaction. This cyclization can be acid-catalyzed or brought about by heating.

References

  1. 1 2 Mascal M, Hafezi N, Wang D, Hu Y, Serra G, Dallas ML, Spencer JP (May 2019). "Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures". Scientific Reports. 9 (1): 7778. Bibcode:2019NatSR...9.7778M. doi:10.1038/s41598-019-44056-y. PMC   6533278 . PMID   31123271.
  2. ↑ Li H, Liu Y, Tian D, Tian L, Ju X, Qi L, et al. (April 2020). "Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease". European Journal of Medicinal Chemistry. 192: 112163. doi:10.1016/j.ejmech.2020.112163. PMID   32109623. S2CID   211564148.
  3. ↑ Jacob, A.; Todd, A. R. (1940). "119. Cannabis indica. Part II. Isolation of cannabidiol from Egyptian hashish. Observations on the structure of cannabinol". J. Chem. Soc. 119: 649–653. doi:10.1039/jr9400000649.
  4. ↑ Merrick J, Lane B, Sebree T, Yaksh T, O'Neill C, Banks SL (2016). "Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid". Cannabis and Cannabinoid Research. 1 (1): 102–112. doi:10.1089/can.2015.0004. PMC   5576596 . PMID   28861485.
  5. ↑ Watanabe K, Itokawa Y, Yamaori S, Funahashi T, Kimura T, Kaji T, Usami N, Yamamoto I (2007). "Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice". Forensic Toxicology. 25: 16–21. doi:10.1007/s11419-007-0021-y. S2CID   2890977.
  6. ↑ Adams R, Pease DC, Cain CK, Clark JH (1940). "Structure of Cannabidiol. VI. Isomerization of Cannabidiol to Tetrahydrocannabinol, a Physiologically Active Product. Conversion of Cannabidiol to Cannabinol". Journal of the American Chemical Society. 62 (9): 2402–2405. doi:10.1021/ja01866a040.
  7. ↑ Adams R, Cain CK, McPhee WD, Wearn RB (1941). "Structure of Cannabidiol. XII. Isomerization to Tetrahydrocannabinols1". Journal of the American Chemical Society. 63 (8): 2209–2213. doi:10.1021/ja01853a052.
  8. ↑ WO 2020/185661,Mascal M, Shevchenko N,"Use of 8,9-dihydrocannabidiol compounds.", assigned to University of California
  9. ↑ Delta 9 Edibles, 1 August 2023
  10. ↑ Mascal, Mark; Hafezi, Nema; Wang, Deping; Hu, Yuhan; Serra, Gessica; Dallas, Mark L.; Spencer, Jeremy P. E. (2019). "Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures". Scientific Reports. 9 (1): 7778. Bibcode:2019NatSR...9.7778M. doi:10.1038/s41598-019-44056-y. PMC   6533278 . PMID   31123271.
  11. ↑ Ben-Shabat, Shimon; Hanuš, Lumír O.; Katzavian, Galia; Gallily, Ruth (2006). "New Cannabidiol Derivatives: Synthesis, Binding to Cannabinoid Receptor, and Evaluation of Their Antiinflammatory Activity". Journal of Medicinal Chemistry. 49 (3): 1113–1117. doi:10.1021/jm050709m. PMID   16451075.
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