Sativex® (nabixomols) is an oromucosal spray with each spray of 100 microliters containing 2.7 mg THC and 2.5 mg CBD. Nabiximols is indicated as treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy. This cannabinoid-based medication is intended to be used in conjunction with the patient’s other anti-spasticity medication. What is the recommended dosing schedule for nabiximols?
“The nabiximols drug monograph suggests to start with 1 spray in the evening. The number of sprays should be gradually increased by 1 spray every other day for the first 4 days and then by 1 spray per day. The sprays should be administered in the morning and at night. “The afternoon/evening dose should be taken at any time between 4 pm and bedtime. When the morning dose is [first] introduced [on day 5], it should be taken at any time between waking and midday. The patient may continue to gradually increase the dose … up to a maximum of 12 sprays* per day, until the patient achieves optimum symptom relief. There should be at least a 15 minute gap between sprays.”
Nabilone is a synthetic cannabinoid that is similar in structure to delta-9-THC and is for oral administration. Nabilone is used for the treatment of chemotherapy-induced nausea and vomiting. What is the recommended dosage of nabilone?
As per the package insert, the usual dose of nabilone is 1 or 2 mg twice daily. The initial dose should be administered 1–3 hours before chemotherapy. Nabilone may be administered daily during the entire chemotherapy cycle 2 or 3 times/day. It is suggested to initiate nabilone therapy with the lower dosage of 1 mg twice daily to minimize adverse effects, and then increase the dose as needed up to a maximum of 2 mg 3 times/day. A dose of 1 or 2 mg may be administered the night prior to chemotherapy.
Dronabinol is an FDA-approved synthetic form of delta-9-THC used for the treatment of anorexia associated with weight loss in adults with AIDS, and for the treatment of nausea and vomiting associated with chemotherapy in patients who have failed conventional antiemetics. What is the recommended dosage of dronabinol?
For adult patients with AIDS, the recommended adult starting dosage of dronabinol is 2.5 mg orally twice daily, one hour before lunch and dinner. For adult patients with n/v associated with chemotherapy, the recommended starting dosage is 5 mg/m2, administered 1 to 3 hours prior to the administration of chemotherapy, then every 2 – 4 hrs. after chemotherapy, for a total of 4 to 6 doses per day. (Beyond this dose, the risk of adverse effects may increase.) It is suggested that the first dose be administered on an empty stomach at least 30 minutes prior to eating; subsequent doses can be taken without regard to meals.
Did Dr. Mechoulam synthesize novel cannabinoids? If so, what is the purpose of these synthetic cannabinoids?
Yes, Dr. Mechoulam’s lab has created synthetic cannabinoids and these cannabinoids have been used as experimental tools and/or have been evaluated to determine the therapeutic potential of cannabinoids. For example, HU-580 is a synthetic methyl ester of cannabidiolic acid (CBDA) created in Dr. Mechoulam’s lab. HU-580 “displays greater potency and a broader bell-shaped dose-response curve than CBDA (or CBD) as an enhancer of the activation of 5-HT1A serotonergic receptors and as an inhibitor of signs of anxiety and of chemotherapy-induced nausea in rats. HU-580 is much more stable than CBDA.” Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
The evidence that mammalian tissues express the CB1 receptor initiated searches for mammalian-produced chemicals that can activate the CB1 receptor. Who was the first group to identify an endogenously produced chemical that binds to a cannabinoid receptor?
Dr. Mechoulam and his lab were the first to identify an endocannabinoid. He led the research that provided convincing evidence that N-arachidonoyl ethanolamine (aka anandamide) is an endogenously produced compound that can activate the CB1 receptor and that 2-arachidonoylglycerol (2-AG), another endogenous compound, activates CB1 and CB2 receptors. Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
Dr. Mechoulam and his collaborators determined that some of the cannabinoids display stereoselectivity. How did the determination of stereoselectivity lead to other advancements in our understanding of cannabinoid science?
The display of stereochemistry of some of the phytocannabinoids led researchers to look for cannabinoid receptors in mammalian tissues. As a result, scientists discovered two G protein-coupled cannabinoid receptors. CB1 was discovered between 1988 and 1990 and CB2 was discovered in 1993. Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
Other than Δ9-THC, did Dr. Mechoulam and his lab isolate other cannabinoids?
Yes. Dr. Mechoulam and his team also reported the isolation, structural elucidation and chemical synthesis of several other cannabinoids, including cannabidiol (CBD), cannabigerol and cannabichromene, and some cannabinoid carboxylic acids. These accomplishments facilitated other cannabinoid research and led to the understanding of the pharmacological actions of the phytocannabinoids. Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
In the early 1960’s, Dr. Mechoulam, along with Dr. Gaoni and other Hebrew University collaborators, were the first to report the isolation, structure elucidation, stereochemistry as well as the activity of Δ9-tetrahydrocannabinol (Δ9-THC). Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
On November 5, 2021, Professor Raphael Mechoulam, PhD celebrates his 91st birthday. What are some of Professor Mechoulam’s accomplishements that have made him an internationally respected and honored scientist?
Dr. Mechoulam is considered to be one of the greatest cannabinoid research scientists of all time. During his nearly 60 years of cannabinoid research, “Raphael Mechoulam has demonstrated…an amazing ability both to come up with exciting original and important ideas that have greatly helped to advance knowledge about cannabinoid preclinical and clinical pharmacology, biochemistry and medicinal chemistry, and to follow these ideas through with great effect. This is due not least to his ability (i) to set up highly talented research teams in his laboratory, to think both as a chemist and as a biologist…(ii) to recognize how his ideas/discoveries might be exploited in the clinic, and then (iii) to set up productive collaborations with clinicians, with preclinical pharmacologists/biologists, and with pharmaceutical companies.” Dr. Mechoulam is also a major contributor to the edcuational mission of www.TheAnswerPage.com focused on the endocannabinoid system and medical cannabis. Visit Dr. Raphael Mechoulam’s new blog posts at: https://www.theanswerpage.com/tap-blog/
Some patients apply CBD topically. Does CBD easily penetrate the skin?
Due to CBD’s large size and hydrophobic properties, CBD does not penetrate the skin efficiently, however, permeation-enhancing gels have been developed. Currently, CBD-containing gels are being evaluated for the treatment of several pediatric disorders, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies.