Years passed, and more studies rolled out with medically beneficial findings regarding cannabis until 2009 when Steep Hill Laboratory in Oakland, California, tested cannabis samples provided by Harborside Health Center to discover that a handful of cultivars contained more CBD than THC. This discovery kicked other labs into gear. They wanted to study medical cannabis to understand and potentially calibrate their cannabinoid ratios. Soon thereafter, laboratories uncovered CBD-dominant strains boasting 20:1 CBD to THC ratios, which opened up the cannabis market for a panoply of CBD products.
Sativex® (GW Pharmaceuticals) is an oromucosal whole cannabis-based spray combining a CB1 partial agonist (THC) with a cannabinoid system modulator (CBD), minor cannabinoids and terpenoids plus ethanol and propylene glycol excipients and peppermint flavoring (McPartland and Russo 2001; Russo and Guy 2006). It was approved by Health Canada in June 2005 for prescription for central neuropathic pain in multiple sclerosis, and in August 2007, it was additionally approved for treatment of cancer pain unresponsive to optimized opioid therapy. Sativex is a highly standardized pharmaceutical product derived from two Cannabis sativa chemovars following Good Agricultural Practice (GAP) (de Meijer 2004), yielding Tetranabinex® (predominantly-THC extract) and Nabidiolex® (predominantly-CBD extract) in a 1:1 ratio. Each 100 μL pump-action oromucosal Sativex spray actuation provides 2.7 mg of THC and 2.5 mg of CBD. Pharmacokinetic data are available, and indicate plasma half lives of 85 minutes for THC, 130 minutes for 11-hydroxy-THC and 100 minutes for CBD (Guy and Robson 2003). Sativex effects commence in 15–40 minutes, an interval that permits symptomatic dose titration. A very favorable adverse event profile has been observed in over 2500 patient years of exposure in over 2000 experimental subjects. Patients most often ascertain an individual stable dosage within 7–10 days that provides therapeutic relief without unwanted psychotropic effects (often in the range of 8–10 sprays per day). In all RCTs, Sativex was adjunctively added to optimal drug regimens in subjects with intractable symptoms, those often termed “untreatable.” Sativex is also available by named patient prescription in the UK and the Catalonia region of Spain. An Investigational New Drug (IND) application to study Sativex in advanced clinical trials in the USA was approved by the FDA in January 2006 in patients with intractable cancer pain.
But he wasn’t finished. In February of 1980, Dr. Mechoulam teamed up with South American researchers to publish a study regarding cannabis and epilepsy. This study is seen as one of the earliest double-blind studies of CBD on clinical subjects. The study Dr. Mechoulam and his team conducted included 16 people, many of whom were children, who all suffered from severe epilepsy. The results were startling: Every subject who received CBD experienced improvement in their condition with little to no side effects. This anticonvulsant study has since proven to be an integral milestone in the world of clinical marijuana research, but largely went unnoticed at the time.
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For epilepsy: A prescription cannabidiol product (Epidiolex) has been used. The recommended starting dose is usually 2.5 mg/kg twice daily (5 mg/kg/day). After one week the dose can be increased to 5 mg/kg twice daily (10 mg/kg/day). If the person doesn't respond to this dose, the maximum recommended is 10 mg/kg twice daily (20 mg/kg/day). In some research, higher doses of up to 50 mg/kg daily have been used. There is no strong scientific evidence that nonprescription cannabidiol products are beneficial for epilepsy.
There’s a growing body of scientific evidence to support the use of topical CBD products to ease pain, inflammation, and the symptoms of arthritis. One study using rats found that topical CBD has “therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects.” More scientific research on humans is needed to confirm all of CBD’s benefits, but the initial research into topical use in humans is also promising.
The glutamatergic system is integral to development and maintenance of neuropathic pain, and is responsible for generating secondary and tertiary hyperalgesia in migraine and fibromyalgia via NMDA mechanisms (Nicolodi et al 1998). Thus, it is important to note that cannabinoids presynaptically inhibit glutamate release (Shen et al 1996), THC produces 30%–40% reduction in NMDA responses, and THC is a neuroprotective antioxidant (Hampson et al 1998). Additionally, cannabinoids reduce hyperalgesia via inhibition of calcitonin gene-related peptide (Richardson et al 1998a). As for Substance P mechanisms, cannabinoids block capsaicin-induced hyperalgesia (Li et al 1999), and THC will do so at sub-psychoactive doses in experimental animals (Ko and Woods 1999). Among the noteworthy interactions with opiates and the endorphin/enkephalin system, THC has been shown to stimulate beta-endorphin production (Manzanares et al 1998), may allow opiate sparing in clinical application (Cichewicz et al 1999), prevents development of tolerance to and withdrawal from opiates (Cichewicz and Welch 2003), and rekindles opiate analgesia after a prior dosage has worn off (Cichewicz and McCarthy 2003). These are all promising attributes for an adjunctive agent in treatment of clinical chronic pain states.

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