Nabiximols

Nabiximols Uses, Dosage, Side Effects, Food Interaction and all others data.

Nabiximols (tradename Sativex®) is a whole plant extract from the Cannabis species Cannabis sativa L. that has been purified into the active components CBD (cannabidiol) and THC (delta-9-tetrahydrocannabinol). For trademark purposes, purified CBD is branded as Nabidiolex®, while THC is purified as the product Tetrabinex®. Sativex® is available in a 1:1 formulation of THC:CBD as an oro-mucosal pump spray used for treatment of neuropathic pain from Multiple Sclerosis (MS) and for intractable cancer pain. Although still largely debated, Cannabis has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity .

From a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon cannabinoid receptors of the body [A32584]. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors found in the human body. While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. While cannabis in its natural plant form is currently used "off-label" for the management of many medical conditions, THC is currently commercially available in synthetic form as Nabilone, as purified isomer as Dronabinol, or in a 1:1 formulation with CBD from purified plant extract as Nabiximols.

The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects .

Nabiximols
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Nabiximols
Generic	Nabiximols
Nabiximols Other Names	Nabiximols
Type
Formula	C₄₂H₆₀O₄
Weight	Average: 628.938 Monoisotopic: 628.449160412
Groups	Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

In Canada, Sativex has received a Notice of Compliance (NOC) for use as an as adjunctive treatment for symptomatic relief of spasticity in patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy.

Sativex has also received a Notice of Compliance with Conditions (NOC/c) for use as an adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis (MS) and 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.

Marketing authorisations with conditions reflect the promising nature of the clinical evidence and the need for confirmatory studies to verify the clinical benefit. Patients should be advised of the conditional nature of the authorizations with conditions.

How Nabiximols works

There is further evidence that CBD also activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .

Volume of Distribution

Cannabinoids are distributed throughout the body; they are highly lipid soluble and accumulate in fatty tissue. The release of cannabinoids from fatty tissue is responsible for the prolonged terminal elimination half-life.

Elimination Route

Individual subject plasma concentration data and pharmacokinetic parameters show a high degree of inter-subject variability.

Following a single buccal administration, maximum plasma concentrations of both CBD and THC typically occur within two to four hours. When administered buccally, blood levels of THC and other cannabinoids are lower compared with inhalation of smoked cannabis. The resultant concentrations in the blood are lower than those obtained by inhaling the same dose because absorption is slower, redistribution into fatty tissues is rapid and additionally some of the THC undergoes hepatic first-pass metabolism to 11-OH-THC, a psycho-active metabolite.

Half Life

Elimination from plasma is bi-exponential with an initial half-life of one to two hours. The terminal elimination half-lives are of the order of 24 to 36 hours or longer.