Mar 22, CBD Has Antioxidant and Neuroprotective Properties. of Health even acknowledges these therapeutic benefits and potential uses of CBD. Dec 1, Are CBD's antioxidant properties the answer to slowing down its own patent on the antioxidant and neuroprotective effects of cannabinoids. Neuroprotective antioxidants from marijuana. Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron Cannabis/chemistry*; Cerebral Cortex/drug effects; Neurons/drug effects; Neuroprotective.
Neuroprotective Benefits and CBD and Antioxidant
Oxidative stress caused by ischemia, traumatic blows, or autoimmune and genetic disorders can cause temporary or permanent neural damage, but studies have shown that CBD is able to protect against this damage and improve recovery. These findings suggest that CBD could be therapeutically beneficial for traumatic brain injuries, spinal cord injuries, spinal cord diseases, and strokes. Federal Tax ID The information contained in this website is for general information and educational purposes only.
It does not constitute medical advice. Therefore, any reliance you place on such information is strictly at your own risk. Please check with your medical doctor before starting or changing your CBD routine.
I accept the terms and conditions and am aware that this notification will not appear again during an unspecified time. What Does That Mean? Why is it important that CBD is an antioxidant? What does it mean that CBD is neuroprotective? Various concentrations of cannabinoids and BHT were included to examine their ability to prevent dihydrorhodiamine oxidation. To confirm that cannabinoids act as antioxidants in the intact cell, neurons were also incubated with the oxidant t-butyl hydroperoxide and varying concentrations of cannabidiol FIG.
The t-butyl hydroperoxide oxidant was chosen for its solubility in both aqueous and organic solvents, which facilitates oxidation in both cytosolic and membrane cell compartments.
Cell toxicity was assessed hours after insult by measuring lactate dehydrogenase LDH release into the culture media. All experiments were conducted with triple or quadruple values at each point and all plates contained positive glutamate alone and baseline controls. The assay was validated by comparison with an XTT based metabolic activity assay. As shown in FIG. The middle cerebral artery of chloral hydrate anesthetized rats was occluded by insertion of suture thread into it.
The animals were allowed to recover from the anesthetic and move freely for a period of two hours. After this time the suture was removed under mild anesthetic and the animals allowed to recover for 48 hours. Then the animals were tested for neurological deficits, sacrificed, and the infarct volume calculated.
To examine the infarct volume, animals were anesthetized, ex-sanguinated, and a metabolically active dye 3-phenyl tetrazolium chloride was pumped throughout the body. All living tissues were stained pink by the dye, while morbid regions of infarcted tissue remained white. Brains were then fixed for 24 hours in formaldehyde, sliced and the infarct volumes measured.
Control animals received injections of vehicle without drug. IV doses would be expected to be times less because of reduction of first pass metabolism. This data shows that infarct size was approximately halved in the animals treated with cannabidiol, which was also accompanied by a substantial improvement in the neurological status of the animal.
These studies with the nonpsychotropic marijuana constituent, cannabidiol, demonstrate that protection can be achieved against both glutamate neurotoxicity and free radical induced cell death. THC, the psychoactive principle of cannabis, also blocked glutamate neurotoxicity with a potency similar to cannabidiol. In both cases, neuroprotection is unaffected by the presence of a cannabinoid receptor antagonist.
These results therefore surprisingly demonstrate that cannabinoids can have useful therapeutic effects that are not mediated by cannabinoid receptors, and therefore are not necessarily accompanied by psychoactive side effects. Cannabidiol also acts as an anti-epileptic and anxiolytic, which makes it particularly useful in the treatment of neurological diseases in which neuroanatomic defects can predispose to seizures e.
A particular advantage of the cannabinoid compounds of the present invention is that they are highly lipophilic, and have good penetration into the central nervous system. The volume of distribution of some of these compounds is at least L in a 70 kg person 1.
The lipophilicity of particular compounds is also about as great as that of THC, cannabidiol or other compounds that have excellent penetration into the brain and other portions of the CNS. Cannabinoids that lack psychoactivity or psychotoxicity are particularly useful embodiments of the present invention, because the absence of such side effects allows very high doses of the drug to be used without encountering unpleasant side effects such as dysphoria or dangerous complications such as obtundation in a patient who may already have an altered mental status.
Cannabidiol and THC have been shown to be comparable to the antioxidant BHT, both in their ability to prevent dihydrorhodamine oxidation and in their cyclic voltametric profiles. Several synthetic cannabinoids also exhibited profiles similar to the BHT, although anandamide, which is not structurally related to cannabinoids, did not. These findings indicate that cannabinoids act as antioxidants in a non-biological situation, which was confirmed in living cells by showing that cannabidiol attenuates hydroperoxide induced neurotoxicity.
The potency of cannabidiol as an antioxidant was examined by comparing it on an equimolar basis with three other commonly used compounds. This unexpected superior antioxidant activity in the absence of BHT tumor promoting activity shows for the first time that cannabidiol, and other cannabinoids, can be used as antioxidant drugs in the treatment including prophylaxis of oxidation associated diseases, and is particularly useful as a neuroprotectant.
The therapeutic potential of nonpsychoactive cannabinoids is particularly promising, because of the absence of psychotoxicity, and the ability to administer higher doses than with psychotropic cannabinoids, such as THC.
This example describes in vitro and in vivo assays to examine the effect of cannabidiol CBD on three lipoxygenase LO enzymes: Enzyme studies were performed using a u. The reaction was initiated by addition of 0. Recordings examined the absorption at nm minus the value at a reference wavelength of nm. Human platelets and leukocytes were purified from buffy coat preparations NIH Blood Bank using a standard Ficoll based centrifugation method used in blood banks.
Prior to use, cells were washed three times to eliminate contaminating cell types. Cultured rat basophillic leukemia cells RBL-2H3 were used as a source of 5-lipoxygenase. Cells were incubated with arachidonic acid and stimulated with the calcium ionophore A Lipids were extracted and separated by reverse phase HPLC.
Product formation was assessed as the area of a peak that co-eluted with an authentic standard, had a greater absorbance at nm than at either or nm, and the formation of which was inhibited by a lipoxygenase inhibitor.
Lipids were extracted with 1 volume of ethyl ether, which was dried under a stream of nitrogen. The ability of HETE s -hydroxy-eicosatetraenoic acid, the product of the action of lipoxygenase on arachidonic eicosatetraenoic acid to protect cortical neurons from NMDAr toxicity was measured as described in Example 3. As shown in FIGS. The leukocyte LO is similar, while the platelet LO is structurally and functionally different, from the porcine LO used in the in vitro enzyme study.
Importantly, this is the first demonstration FIG. Although the mechanism of this protection is unknown at the present time, HETE is known to be an important neuromodulator, due to its ability to influence potassium channel activity. The present invention includes a treatment that inhibits oxidation associated diseases in a subject such as an animal, for example a rat or human.
The method includes administering the antioxidant drugs of the present invention, or a combination of the antioxidant drug and one or more other pharmaceutical agents, to the subject in a pharmaceutically compatible carrier and in an effective amount to inhibit the development or progression of oxidation associated diseases.
Although the treatment can be used prophylactically in any patient in a demographic group at significant risk for such diseases, subjects can also be selected using more specific criteria, such as a definitive diagnosis of the condition.
The administration of any exogenous antioxidant cannabinoid would inhibit the progression of the oxidation associated disease as compared to a subject to whom the cannabinoid was not administered. The antioxidant effect, however, increases with the dose of the cannabinoid. The vehicle in which the drug is delivered can include pharmaceutically acceptable compositions of the drugs of the present invention using methods well known to those with skill in the art.
Any of the common carriers, such as sterile saline or glucose solution, can be utilized with the drugs provided by the invention.
Routes of administration include but are not limited to oral, intracranial ventricular icv , intrathecal it , intravenous iv , parenteral, rectal, topical ophthalmic, subconjunctival, nasal, aural, sub-lingual under the tongue and transdermal. The antioxidant drugs of the invention may be administered intravenously in any conventional medium for intravenous injection such as an aqueous saline medium, or in blood plasma medium.
Such medium may also contain conventional pharmaceutical adjunct materials such as, for example, pharmaceutically acceptable salts to adjust the osmotic pressure, lipid carriers such as cyclodextrins, proteins such as serum albumin, hydrophilic agents such as methyl cellulose, detergents, buffers, preservatives and the like. Given the low solubility of many cannabinoids, they may be suspended in sesame oil. Given the excellent absorption of the compounds of the present invention via an inhaled route, the compounds may also be administered as inhalants, for example in pharmaceutical aerosols utilizing solutions, suspensions, emulsions, powders and semisolid preparations of the type more fully described in Remington: The Science and Practice of Pharmacy 19 th Edition, in chapter Embodiments of the invention comprising pharmaceutical compositions can be prepared with conventional pharmaceutically acceptable carriers, adjuvants and counterions as would be known to those of skill in the art.
The compositions are preferably in the form of a unit dose in solid, semi-solid and liquid dosage forms such as tablets, pills, powders, liquid solutions or suspensions, injectable and infusible solutions, for example a unit dose vial, or a metered dose inhaler. If the antioxidant drugs are to be used in the prevention of cataracts, they may be administered in the form of eye drops formulated in a pharmaceutically inert, biologically acceptable carrier, such as isotonic saline or an ointment.
Conventional preservatives, such as benzalkonium chloride, can also be added to the formulation. In ophthalmic ointments, the active ingredient is admixed with a suitable base, such as white petrolatum and mineral oil, along with antimicrobial preservatives. Specific methods of compounding these dosage forms, as well as appropriate pharmaceutical carriers, are known in the art.
The Science and Practice of Pharmacy, 19th Ed. The compounds of the present invention are ideally administered as soon as a diagnosis is made of an ischemic event, or other oxidative insult. For example, once a myocardial infarction has been confirmed by electrocardiograph, or an elevation in enzymes characteristic of cardiac injury e. CKMB , a therapeutically effective amount of the cannabinoid drug is administered. A dose can also be given following symptoms characteristic of a stroke motor or sensory abnormalities , or radiographic confirmation of a cerebral infarct in a distribution characteristic of a neurovascular thromboembolic event.
The dose can be given by frequent bolus administration, or as a continuous IV dose. The following table lists examples of some dibenzopyran cannabinoids that may be useful as antioxidants in the method of the present invention. R-group substituents are H if not indicated otherwise. Chemical structures of some of the dibenzopyran cannabinoids are shown below.
The following table lists examples of some cannabinoids which are structural analogs of cannabidiol and that may be useful as antioxidants in the method of the present invention. A particularly useful example is compound CBD, cannabidiol. The invention being thus described, variation in the materials and methods for practicing the invention will be apparent to one of ordinary skill in the art.
Such variations are to be considered within the scope of the invention, which is set forth in the claims below. Year of fee payment: Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases.
The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia.
Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula I wherein the R group is independently selected from the group consisting of H, CH 3 , and COCH 3.
A method of treating diseases caused by oxidative stress, comprising administering a therapeutically effective amount of a cannabinoid that has substantially no binding to the NMDA receptor to a subject who has a disease caused by oxidative stress. The method of claim 1 , wherein the cannabinoid is nonpsychoactive.
The method of claim 1 , wherein the cannabinoid is not an antagonist at the NMDA receptor. The method of claim 1 , wherein the cannabinoid is: The method of claim 5 , wherein R is H, substituted or unsubstituted alkyl, carboxyl or alkoxy.
The method of claim 2 , wherein the cannabinoid is: A is cyclohexyl, substituted or unsubstituted aryl, or. R 1 is H, substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl;. R 3 is of H, lower substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl;.
R 4 is H, hydroxyl, or lower substituted or unsubstituted alkyl; and. The method of claim 7 , wherein. R 2 is unsubstituted C 1 -C 5 alkyl, hydroxyl, methoxy or ethoxy;. The method of claim 9 , wherein the cannabinoid is: The method of claim 10 , wherein the cannabinoid is cannabidiol. A method of treating an ischemic or neurodegenerative disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a cannabinoid, where the cannabinoid is.
The method of claim 15 , wherein the cannabinoid is not a psychoactive cannabinoid. The method of claim 15 where the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease.
A method of treating a disease with a cannabinoid that has substantially no binding to the NMDA receptor, comprising determining whether the disease is caused by oxidative stress, and if the disease is caused by oxidative stress, administering the cannabinoid in a therapeutically effective antioxidant amount. The method of claim 18 , wherein the cannabinoid has a volume of distribution of at least 1. The method of claim 1 , wherein the cannabinoid selectively inhibits an enzyme activity of 5- and lipoxygenase more than an enzyme activity of lipoxygenase.
A method of treating a neurodegenerative or ischemic disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a compound selected from any of the compounds of claims 9 through The method of claim 22 where the compound is cannabidiol.
The method of claim 22 , wherein the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease. The method of claim 24 wherein the disease is an ischemic infarct. The method of claim 1 , wherein the cannabinoid is not an antagonist at the AMPA receptor. Compounds for delivering amino acids or peptides with antioxidant activity into mitochondria and use thereof.
Cannabidiol for use in the treatment of transmissible neurodegenerative conditions. Use of cannabinoid receptor agonists as hypothermia inducing drugs for the treatment of ischemia. Cannabinoids for use in treating or preventing cognitive impairment and dementia. Pharmaceutical compositions comprising a statin and a cannabinoid and uses thereof.
Therapeutic methods and agents for diseases associated with decreased expression of aop-1 gene or aop Compounds having unique CB1 receptor binding selectivity and methods for their production and use.
Compositions of a cyclooxygenase-2 selective inhibitor and a cannabinoid agent for the treatment of central nervous system damage. Prodrugs of cannabidiol, compositions containing prodrugs of cannabidiol and methods of use thereof. Yissum Research Development Co. NMDA-Blocking compounds, pharmaceutical compositions, their preparation and use.
Method for the production of 6,dihydrohydroxy-cannabidiol and the use thereof for the production of trans-deltatetrahydrocannabinol. Pyrazole derivatives, process for their preparation and pharmaceutical compositions containing them. Neuroprotective pharmaceutical compositions of 4-phenylpinene derivatives and certain novel 4-phenylpinene compounds. Amides of mono and bicarboxylic acids with amino acids or glycosamines, selectively active on the cannabinoid peripheral receptor.
Pyrazole derivatives, method for preparing same, and pharmaceutical compositions containing said derivatives. Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease. Method of administering narcotic antagonists and analgesics and novel dosage forms containing same.
Nonclassical cannabinoid analgetics inhibit adenylate cyclase: Controlling nitrogen oxide concentrations to modulate skeletal muscle contraction. Superoxide generation during cardiopulmonary bypass: Fullerene derivatives that modulate nitric oxide synthase and clamodulin activity. Inhibitory effects of tannins on hyaluronidase activation and on the degranulation from rat mesentery mast cells.
Stable composition for inhalation therapy comprising deltatetrahydrocannabinol and semiaqueous solvent therefor. Increased oxygen radical formation and mitochondrial dysfunction mediate beta cell apoptosis under conditions of AMP-activated protein kinase stimulation.
US6630507B1 - Cannabinoids as antioxidants and neuroprotectants - Google Patents
Apr 26, Neuroprotective effects of CBD in hypoxic–ischemic brain damage model .. of antioxidant and cannabinoid receptor-independent properties. Apr 27, The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat Antioxidants such as α-tocopherol (5, 6) are effective . To examine the effects of cannabinoids on ROS toxicity, 7- to day-old. Mechanisms proposed for the neuroprotective effects exerted by CBD in .. Wink D, Rosenthal R, Axelrod J. Neuroprotective antioxidants from marijuana.