13956-29-1 Usage
Uses
Used in Pharmaceutical Applications:
CANNABIDIOL is used as a therapeutic and pharmaceutical drug target for its various bioactivities, such as anticonvulsant, anxiolytic, and anti-inflammatory effects.
Used in Research and Forensic Applications:
CANNABIDIOL is used as a certified reference material for research and forensic applications, due to its non-psychoactive nature and its role as a major phyto-cannabinoid.
Used in Neuroprotection and Anti-Inflammatory Applications:
CANNABIDIOL is used as a neuroprotective and anti-inflammatory agent, showing potential in treating various conditions related to inflammation and neurodegeneration.
Used in Antioxidant Applications:
CANNABIDIOL is used as an antioxidant, potentially benefiting the body's response to oxidative stress and related conditions.
Used in Analgesic Applications:
CANNABIDIOL is used as an analgesic, potentially providing pain relief for various conditions.
Used in Muscle Relaxant Applications:
CANNABIDIOL is used as a muscle relaxant, potentially helping to alleviate muscle tension and related discomfort.
Used in Antipsychotic Applications:
CANNABIDIOL is used as an antipsychotic, potentially aiding in the treatment of certain psychiatric conditions.
Used in Sedative and Hypnotic Applications:
CANNABIDIOL is used as a sedative and hypnotic, potentially promoting relaxation and sleep.
Receptors
So far, two membrane receptors for cannabidiol, both coupled to G protein and named CB1 and CB2, have been identified. While CB1 receptors are mainly expressed in the central and the peripheral nervous systems, CB2 receptors have been reported to be more abundantly detected in cells of the immune system[5]. Moreover, two orphan G protein-coupled receptors, GPR119 and GPR55, possibly activated by multiple different cannabinoid ligands[6], have been recently proposed as novel cannabinoid receptors.
Indication
Being used in combination with delta-9-tetrahydrocannabinol as the product Sativex, cannabidiol was applied for the following indications: 1)?as adjunctive treatment for symptomatic relief of spasticity in adult patients with multiple sclerosis[MS] who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy [7]; Sativex was also given a Notice of Compliance with Conditions(NOC/c)?by Health Canada for the following indications: 1)?as adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis; 2)?as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain[7].
Pharmacodynamics
The correct use of CBD in human therapy necessarily requires basic information related to pharmacokinetics. Cannabis derivatives are usually inhaled or orally administered. Other routes, including rectal, transdermic, eye drops, aerosols and intravenous have been used in a small number of studies so that the relevance of findings is limited. Recently, it was demonstrated in rabbits that sublingual administration of a solid CBD/beta-cyclodextrin complex might provide an alternative formulation for sublingual administration[8]. The pharmacokinetics of CBD is quite complicated and in many aspects resembles that of Δ9-THC. Once taken orally, CBD bioavailability ranges between 13% and 19%, due to a marked first-pass effect, while the systemic bioavailability of inhaled CBD in a group of cannabis users was 31%(range 11– 45%). The plasma pattern was similar to that of Δ9-THC. Daily oral doses of CBD 10 mg/kg/day chronically administered resulted in mean plasma concentrations of 5.9–11.2 ng/mL[9]. CBD is rapidly distributed when intravenously administered, and easily passes the blood–brain barrier. CBD shows a prolonged elimination; its terminal half-life is about 9 h, and it is excreted preferentially in the urine, both free and as its glucuronide compound[10]. Cannabidiol impairs hepatic drug metabolism in several animal species, and inhibits mouse hepatic metabolism through the inactivation of specific cytochrome P450 belonging to the 2C and 3A subfamilies[11]. The metabolism of CBD showed biotransformation routes typically observed for cannabinoids[12]. It undergoes multiple hydroxylations, oxidations to carboxylic acids, beta-oxidation, conjugation and epoxidation[13]. Conjugation with fatty acids, first observed with Δ9and Δ8-THC, provides a potent means of increasing the lipophilicity and, hence, tissue accumulation[14]. CBD-7-oic acid together with CBD glucuronide represent the most abundant products of CBD metabolism detected in human urine[13]. Unlike Δ9-THC a remarkable percentage of unchanged CBD is excreted in the faeces[15].
Pharmacology
Cannabinoid pharmacology is a field rapidly expanding and the therapeutic properties of cannabinoid receptor agonists include analgesia, muscle relaxation, immunosuppressant, antiinflammatory and antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilatation, neuroprotection and antineoplastic effects[16]. Despite the emerging evidence regarding therapeutic activities of CBs, their effective introduction in clinical use is still controversial and strongly limited by the unavoidable psychotropic effects exhibited by many of them. Since it was previously demonstrated that CBD binds with a low affinity to both CB1 and CB2 cannabinoid receptors, much research was aimed at recognizing CB1 and CB2 independent modes of action for this phytocannabinoid. To date, different molecular targets have been proposed. The first evidence that CBD can bind to sites different from cannabinoid receptors was offered by the observation that natural CBD and the[+]-synthetic one both stimulate the type-1 vanilloid receptor[17]. Other studies indicated that CBD also binds to 5-HT1A and such an interaction was suggested to account for the attenuation of cerebral infarction size occurring during ischemia[18] and also for its anxiolytic effect[19]. It has been also reported that CBD may behave as an allosteric modulator at μ and δ opioid receptors, even if the effects occur at very high levels of phytocannabinoid, so that this modulation cannot be expected to contribute markedly to the CBD actions exerted in vivo[20]. However, although CBD displays very low affinity for both CB1 and CB2, it has been reported recently that it can operate as a CB2 receptor inverse agonist and this may, at least in part, contribute to its widely documented antiinflammatory properties[21].
Furthermore it is commonly recognized that many CBD effects are mainly due to its antioxidant activity as first demonstrated by Hampson et al.(1998)[22] that exposed rat cortical neuron cultures to a toxic level of the excitatory neurotransmitter glutamate. On that occasion, the authors showed that CBD exerted a potent antioxidant activity, resulting in a more protective effect than either ascorbate or α-tocopherol, against glutamate-mediated neurotoxicity.
Pharmacology
Cannabidiol, a constituent of the cannabis plant, has been receiving considerable attention of late for its potential therapeutic utility, including potential anxiolytic, anticonvulsant,anti-inflammatory, and neuroprotective effects. Cannabidiol has a complex pharmacology. In contrast to THC, cannabidiol has minimal affinity for CB1 and CB2 receptors and produces no intoxication. The effects of cannabidiol in combination with THC have been mixed, with some data suggesting it may reduce THC’s mood-altering and cognitive effects, while others show no effect. If oral cannabidiol reduces cannabis intoxication, it could be a potential medication to treat CUD. However, Haney et al. tested a range of cannabidiol doses (200–800 mg) in combination with active and placebo cannabis and found no cannabidiol effect on the subjective, reinforcing, or cardiovascular effects of smoked cannabis, providing little support for cannabidiol’s utility as a medication to reduce cannabis’ positive reinforcing and subjective effects.
Mechanism of neuroprotective effect
The neuroprotective actions of CBD, mainly due to its antiinflammatory and antioxidant properties, have been well documented[22]. Recently, a neuroprotective mechanism of CBD has also been confirmed in a mouse model of ischemia, where CBD explicates the cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism[23], in addition to a 5HT1A receptor action[18]. It has also been demonstrated that CBD reverses binge ethanol-induced neurotoxicity, once again, via a cannabinoid receptor independent antioxidant mechanism[24]. The potential of CBD to attenuate the excessive formation of peroxynitrites induced by glutamate also contributes to its neuroprotective effects, as demonstrated by the in vitro results pointing to the ability of CBD to induce the prevention of retinal apoptosis[25].
Toxicity
Cannabidiol exhibits very low toxicity in humans and in other species: the LD50 after intravenous administration to rhesus monkeys was 212 mg/kg[26]. The oral LD50 has not been established, but in 1981 Rosenkrantz showed that an oral dose of CBD 20–50 times larger than the intravenous route is required to initiate severe intoxication[26]. CBD does not cause relevant CNS alterations. Moreover, a large body of studies failed to reveal teratogenic or mutagenic effects induced by CBD[27, 28].
Biological Activity
Non-psychotropic constituent of cannabis that is anticonvulsive, antihyperalgesic and neuroprotective in vivo . GPR55 and weak CB 1 antagonist (IC 50 values are 0.445 and 3.35 μ M), CB 2 receptor inverse agonist and inhibitor of anandamide uptake (IC 50 = 27.5 μ M). Also a weak agonist at VR1 vanilloid receptors (EC 50 = 3.5 μ M).
Check Digit Verification of cas no
The CAS Registry Mumber 13956-29-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,3,9,5 and 6 respectively; the second part has 2 digits, 2 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 13956-29:
(7*1)+(6*3)+(5*9)+(4*5)+(3*6)+(2*2)+(1*9)=121
121 % 10 = 1
So 13956-29-1 is a valid CAS Registry Number.
InChI:InChI=1/C21H30O2/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/h11-13,17-18,22-23H,2,5-10H2,1,3-4H3/t17-,18+/m0/s1
13956-29-1Relevant articles and documents
Stereoselective Synthesis of Nonpsychotic Natural Cannabidiol and Its Unnatural/Terpenyl/Tail-Modified Analogues
Anand, Radhika,Cham, Pankaj Singh,Gannedi, Veeranjaneyulu,Sharma, Sumit,Kumar, Mukesh,Singh, Rohit,Vishwakarma, Ram A.,Singh, Parvinder Pal
, p. 4489 - 4498 (2022/04/07)
Here, we report a three-step concise and stereoselective synthesis route to one of the most important phytocannabinoids, namely, (-)-cannabidiol (-CBD), from inexpensive and readily available starting material R-(+)-limonene. The synthesis involved the diastereoselective bifunctionalization of limonene, followed by effective elimination leading to the generation of key chiral p-mentha-2,8-dien-1-ol. The chiral p-mentha-2,8-dien-1-ol on coupling with olivetol under silver catalysis provided regiospecific (-)-CBD, contrary to reported ones which gave a mixture. The newly developed approach was further extended to its structural analogues cannabidiorcin and other tail/terpenyl-modified analogues. Moreover, its opposite isomer (+)-cannabidiol was also successfully synthesized from S-(-)-limonene.
CANNABIS EXTRACTS AND USES THEREOF
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, (2022/03/14)
The present disclosure concerns a group of cannabinoid compounds defined by formulas (I) to (IV), wherein R1 is —H or —COOH, for the first time isolated and fully characterized in structure, absolute stereochemistry by the present applicant. Methods of isolation, characterization, stereoselective synthesis, biological activity, pharmaceutical compositions and therapeutic applications of the present compounds as modulators of the cannabinoid CB1 receptor are also object of the disclosure.
BIOACTIVE PHENOLATE IONIC COMPLEXES
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Page/Page column 50, (2021/10/30)
The invention provides an isolated material, or a phenolate form of at least one phenol- containing active material, wherein the isolated material comprises one or more phenolate species and a counter ion (a cation) in the form of a metal salt, a phosphonium or an ammonium.
A Novel and Practical Continuous Flow Chemical Synthesis of Cannabidiol (CBD) and its CBDV and CBDB Analogues
Chiurchiù, Elena,Sampaolesi, Susanna,Allegrini, Pietro,Ciceri, Daniele,Ballini, Roberto,Palmieri, Alessandro
supporting information, p. 1286 - 1289 (2021/02/05)
Cannabidiol is one of the main non-psychoactive cannabinoids present in Cannabis sativa and, in the last decade, it is gaining great interest among the scientific community for its pharmaceutical, nutraceutical, and cosmetic applications. Herein, we report the first continuous flow chemical synthesis of cannabidiol (CBD) and its analogues cannabidivarin (CBDV) and cannabidibutol (CBDB). This approach permits to synthesize products in very good yields (55–59 %), limiting the formation of psychoactive and illegal cannabinoids such as tetrahydrocannabinol (THC).
Method for preparing cannabinoids
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Page/Page column 8-10, (2021/04/21)
Provided is a method for preparing synthetic cannabidiol, including hydrolysis-decarboxylation of a compound represented by formula (II) in a solvent-free state under atmospheric pressure. The method further includes preparation of the compound represented by formula (II). The method provides a safe, economical, environmentally friendly and scalable method for synthetic preparation of cannabidiol.
Method for continuously preparing cannabidiol intermediate through green photooxidation
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Paragraph 0077-0112, (2021/05/19)
The invention provides a method for continuously preparing a cannabidiol intermediate compound (4R)-1-methyl-4-(2-(1-propylene))-2-cyclohexene-2-ol (formula III) through photooxidation, which comprises the following steps: taking (R)-(+)-limonene (formula I-a) as an initial raw material, carrying out continuous photooxidation reaction in a photoreactor to obtain peroxide, and then carrying out reduction reaction to obtain an intermediate III. The technical route is simple and easy to implement, conditions are mild, column separation and purification are not needed, the production cost is greatly reduced, and industrial production is convenient to implement. The cannabidiol intermediate compound III is prepared by using a simple synthesis route, and the method has the advantages of simple process, less pollution, easiness in purification and the like.
Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB2Receptor Derived from the Natural Product Cannabidiol
Navarro, Gemma,Gonzalez, Angel,Sánchez-Morales, Adrià,Casajuana-Martin, Nil,Gómez-Ventura, Marc,Cordomí, Arnau,Busqué, Félix,Alibés, Ramon,Pardo, Leonardo,Franco, Rafael
, p. 9354 - 9364 (2021/07/19)
Cannabidiol (CBD), the second most abundant of the active compounds found in the Cannabis sativa plant, is of increasing interest because it is approved for human use and is neither euphorizing nor addictive. Here, we design and synthesize novel compounds taking into account that CBD is both a partial agonist, when it binds to the orthosteric site, and a negative allosteric modulator, when it binds to the allosteric site of the cannabinoid CB2 receptor. Molecular dynamic simulations and site-directed mutagenesis studies have identified the allosteric site near the receptor entrance. This knowledge has permitted to perform structure-guided design of negative and positive allosteric modulators of the CB2 receptor with potential therapeutic utility.
STABLE CANNABINOID COMPOSITIONS
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, (2022/01/08)
The present application discloses powder and aqueous formulations. These include but are not limited to water dispersible cannabinoid formulations, especially those comprising cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) as well as other cannabinoids. Generally, these embodiments do not include major amounts of Tetrahydrocannabinol (THC), but certain embodiments are envisioned that do contain measurable concentrations of THC. Embodiments may include one or more emulsifiers selected from the group consisting of Tween (polysorbate) 20, Tween 60, Tween 80, Span 20, Span 60, Span 80, Poloxamer 188, Vit E-TPGS (TPGS), TPGS-1000, TPGS-750-M, Solutol HS 15, PEG-40 hydrogenated castor oil, PEG-35 Castor oil, PEG-8-glyceryl capylate/caprate, PEG-32-glyceryl laurate, PEG-32-glyceryl palmitostearate, Polysorbate 85, polyglyceryl-6-dioleate, sorbitan monooleate, Capmul MCM, Maisine 35-1, glyceryl monooleate, glyceryl monolinoleate, PEG-6-glyceryl oleate, PEG-6-glyceryl linoleate, oleic acid, linoleic acid, propylene glycol monocaprylate, propylene glycol monolaurate, polyglyceryl-3 dioleate, polyglyceryl-3 diisostearate and lecithin.
Preparation method of cannabidiol
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Paragraph 0050-0051, (2021/11/06)
The invention discloses a preparation method of cannabidiol. To the method, malonate type compounds and hexanal serve as starting materials, Knoevenagel condensation reaction is carried out under basic conditions to obtain compound (3). The obtained compound (3) and the acetoacetate compound undergo Michael addition and intramolecular Aldol condensation reaction under basic conditions to obtain compound (5). Compound (5) is subjected to oxidative aromatization to give compound (6). Compound (6) and (+) - trans - are subjected to -2-8 - alkylation to give compound (-1 -) under acidic conditions to mint Friedel, Crafts diene 8 alcohol. The finally obtained compound (8) is subjected to high-temperature hydrolysis decarboxylation to obtain the target compound cannabidiol (CBD) under an alkaline condition, and has the CBD) high reaction selectivity, no isomer formation, high total yield, less byproducts, easy purification of the product, low process cost and easy realization of industrial production.
Synthetic method of cannabidiol
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Paragraph 0023-0028, (2021/04/03)
The invention discloses a synthetic method of cannabidiol, wherein the synthetic method specifically comprises the steps: carrying out a coupling reaction on a raw material A and (1S,4R)-1-methyl-4-(1-methyl vinyl)-2-cyclohexene-1-ol under the catalysis of an acid catalyst to obtain an intermediate I or an intermediate II; converting hydroxyl in the intermediate II into a halide-like compound to obtain an intermediate III; and carrying out Suzuki coupling on the intermediate I or the intermediate III and pentyl boride to obtain the final product cannabidiol. The reaction system is simple, thereaction temperature is within 100 DEG C, the reaction conditions are easy to control, and large-scale production is easy; the cannabidiol intermediate prepared by the method disclosed by the invention can be recrystallized and purified by a conventional method, the yield is up to 86.5%, the purity is up to 98.7%, and the chemical purity and single impurity index requirements of the cannabidiol intermediate serving as a key intermediate of a crude drug can be met; the yield of the cannabidiol prepared by the method is as high as 80.7%, the purity is as high as 97%, the raw material indexes arecompletely met, and a new method and thought are provided for industrial production of the cannabidiol.
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