____________________________________________________ Medical Marijuana and Other Cannabinoids
Dronabinol Dronabinol (branded as Marinol) is an isomer of THC, and across a wide range of oral doses, it is shown to be chemically identical to plant-derived THC [37]. Dronabinol was initially approved by the U.S. Food and Drug Administration (FDA) in 1985 for the treatment of chemotherapy-induced nausea and vomiting in patients lacking adequate response to existing antiemetics, and then in 1992 for anorexia and cachexia in patients with AIDS. Dronabinol is a Schedule III substance and is available in 2.5–10 mg oral capsules and 5 mg/mL oral solution [83]. Nabilone Nabilone (Cesamet) is a Schedule II THC analog that is chemically similar but not identical to THC [37]. Approved by the FDA in 1985 for the treatment of chemotherapy- induced refractory nausea and vomiting and used off-label for analgesia, it is considered more potent than synthetic THC (e.g., dronabinol) [84]. It is administered (1 mg oral capsule) in doses of 1–2 mg twice daily for adults and 0.5–1 mg twice daily for pediatric patients [83]. Nabiximols Nabiximols (Sativex) is a botanically derived cannabis extract with a defined 1:1 ratio of THC to CBD (27 mg/mL THC + 25 mg/mL CBD) delivered as a metered buccal spray. This drug has regulatory approval for select pain indications in 20 countries (including Canada) and is currently undergoing advanced phase III trials in the United States for treatment of cancer pain refractory to optimal opioid therapy and for treatment of multiple sclerosis spasticity [83; 85]. Cannador Cannador is an orally administered cannabis extract contain- ing a 2:1 ratio of THC to CBD. It is under investigation in Europe by the Institute for Clinical Research for the treatment of anorexia/cachexia in patients with cancer [86]. Pharmaceutical-Grade Smoked Cannabis Smoked cannabis here applies to the medicinal cannabis produced in Canada and the Netherlands, because the excep- tional quality, purity, and consistency controls are in line with pharmaceutical-level standards. In both countries, cannabis for medical or research use is grown by a single contractor, licensed by the government, under exceptionally strict, controlled, and documented conditions. From “seed to smoke,” the seedlings are grown, packaged, and distributed via a centralized supply chain.
in combination with cannabinoid receptor agonists, on CB1 and CB2 signaling in vitro [76]. The terpenoids were tested both individually and in combination for periods of up to 30 minutes. None of the six terpenoids tested directly activated CB1 or CB2 or modulated the signaling of THC [76]. A study that included five common terpenoids from Cannabis also found that none had direct interactions with CB1 or CB2 [77]. Flavonoids Cannabis flavonoids are natural plant constituents also found in whole cannabis extracts. Beneficial activities from flavo- noids include inhibition of TNF- α by apigenin, a potentially therapeutic mechanism in multiple sclerosis and rheumatoid arthritis; and PGE2 inhibition by cannflavin A, an action 30 times greater than PGE2 inhibition by aspirin [78]. One study evaluated the neuroprotective and anti-aggregative properties of cannflavin A and found that it demonstrated a neuroprotective role against the amyloid β -mediated neurotoxicity associated with Alzheimer disease [79]. Phytosterols A number of phytosterols are present in cannabis, with specific effects associated with each. For example, the cannabis phytos- terol β -sitosterol was found to reduce topical inflammation by 65% and chronic edema by 41% in skin models [80]. Cannabis root contains significant amounts of β -sitosterol and other sterols that can be extracted by various methods [81]. Extracts of cannabis root have been used to treat pain and inflamma- tion for millennia by various cultures, including the Romans as described by Pliny the Elder.
PHARMACEUTICAL CANNABINOID PREPARATIONS
Following identification of THC as the primary active con- stituent in cannabis, investigative focus primarily involved the therapeutic potential of isolated THC. Although efficacy was found across many pathologic conditions, the promi- nent psychotropic effects of THC limited its clinical appeal. Discovery of the ECS and characterization of additional phytocannabinoids prompted research evaluation of the therapeutic potential of other phytocannabinoids lacking the psychotropic effects of THC. Investigation of CBD, cannab- igerol, Δ 9-tetrahydrocannabivarin, and cannabidivarin led to promising results in preclinical models of CNS disease. This research also revealed the basis for expanded receptor targeting beyond CB receptors with these agents and the suggestion of clinical utility in epilepsy, neurodegenerative diseases, affective disorders, and central modulation of feeding and appetitive behavior [82]. These findings have influenced the direction of modern cannabinoid drug development and evaluation. Many novel cannabinoid therapeutics are in early-stage safety and efficacy evaluation, and the following cannabinoids are in current clinical or advanced-phase investigative use.
127
EliteLearning.com/Dental
Powered by FlippingBook