Cannabinoids are a diverse class of chemical compounds that occur naturally in the human body (endocannabinoids) and cannabis plants (phytocannabinoids). Interactions with the endocannabinoid system (ECS) trigger the release of neurotransmitters triggering various physiological changes.
There are up to 113 different types of Cannabinoids such as CBG, CBC, CBD, THC, CBN and CBDL, all of which are used for different therapeutic or recreational reasons due to their difference in chemical structures and receptors where they bind.
For instance, CBD, CBG and CBC are non-psychoactive agents yet THC, CBN and CBDL are known for their psychoactive properties and bind mainly to CB1. There are three main subgroups: endocannabinoids, phytocannabinoids and artificially made synthetics.
Phytocannabinoids include Cannabidiol (CBD), one of the most abundant types of Cannabinoids found in and extracted from industrial hemp. It has anti-inflammatory, antioxidant, analgesic and anti psychotic properties thus is used to treat vomiting and nausea, epilepsy, oxidative injury and anxiety. Tetra-hydrocannabinol (THC), on the other hand is the рrіmаrу psychoactive Cаnnаbіnоіd found in cannabis is used for palliating neuropathic pain, overactive bladder and spasticity. THC has a strong affinity to and activates CB1 whereas CBD does not. CBD can counteract the psychoactivity of THC due to its relations to CB1 and CB2.
The receptors CB1 and CB2, both coupled with g-proteins, have a significant role in the mechanism of Cannabinoids. CB1 is located in the brain region and CNS, where it impacts the limbic system by converting signals as an outcome to CNS-active components of Cannabis. CB2 is primarily expressed in the immune system and peripheral nerve terminals, playing a role in antinociception.
Endocannabinoids are naturally manufactured endogenous ligands in the body and include 2-arachidonoylglycerol and palmitoylethanolamide. Some are released from depolarised neurons and bind to CB1 receptors in the pre-synaptic neuron. This will cause a reduction in the release of GABA or glutamate, leading to short-term plasticity. Therefore, the CB1 receptor is the psychoactive cannabinoid receptor. Contrarily, CB2 does not have a psychoactive effect as it is mainly located in peripheral organs thus is able to influence fundamental body functions.
Marinol is a synthetic and pharmaceutical stereo isomer of THC(delta-9-tetrahydrocannabinol)and used as an appetite stimulant for treating individuals with HIV/AIDS and a form of treatment for chemotherapy-induced nausea and vomiting.
ØRoutes of Administration:
Marinol is administrated through oral capsules containing 2.5 mg, 5 mg, or 10 mg of dronabinol. This is a convenient route and allows for an enhanced effect of non-absorbed drugs on the GI tract.
ØPharmacokinetics Absorption: Around 90%–95% of Marinol is absorbed after a single dosage capsule. However, as a consequence of first pass high lipid solubility and hepatic metabolism, 10%–20% of the administrated dose is able to get to the systemic circulation.
Distribution:
The distribution of Marinol is the movement of drug between blood and extra vascular tissues. The plasma protein binding of dronabinol is approximately 97% and around 10L/kg of Marinol is distributed due to the substances lipid solubility.
Metabolism: Marinol is metabolized to 11-OH-delta-9-THC as it goes through a considerable first-pass hepatic metabolism via Microsomal hydroxylation. Cytochrome p450, enzymes CYP2C9 and CYP2C19 allow for this action to occur producing both active and inactive metabolites. The concentration of these metabolites is highest at around 0.5 to 4 hours after oral consumption.
Excretion:
Over 55% of the Marinol along with its bio transformation by-products are excreted in faeces and around 10%-15% is detected from urine after 72 hours. Furthermore, less that 5% is recovered in the faeces unchanged. After 5 weeks and a single dose of the Marinol, low levels of metabolites are still found in the urine and faeces. The primary metabolite found in urine is ester glucuronic acid and THC-COOH whereas in the faeces mainly 11-OH-THC is found.
ØPharmacodynamics Mechanism of action:
Marinol has a complex effect on the CNS and its central sympathomimetic activity. They are stereo isomers of THC thus have partially agonist properties at CB1 and CB2. Their psychoactive effects are mainly mediated by the activation of CB1. This decreases the concentration of cAMP signal transaction is exerted by Cannabinoid receptors, leading to a decreased neuron excitability.
Marinol inhibits vomiting by effecting the control mechanism in the medulla oblongata. They are able to generate antiemetic effects by either altering the upper cortex, which in turn influences the medulla or mediating Cannabinoid receptors in the ASNTS, a region directly connected to the hypothalamus. They are also able to influence antiemetic effects by acting to oppose the effects of serotonin (5-HT3). This will inhibit the release of neurotransmitters from vagal afferent terminals that induce vomit.The CB1 receptors in the lateral hypothalamus will also affect the appetite stimulating properties of this drug. Furthermore, it can also be mediated by ASNTS.
-Marinol shows a reversible effect on appetite, cognition, mood and perception. This is related to the dosage, where there is a positive correlation between an increasing frequency and dosage.
-It has an onset of action of 0.5 to 1 hours and peak effect at 2 to 4 hours. The psychoactive results last 4 to 6 hours. Furthermore, its appetite stimulant effects last for over 24 hours after a single dose usage.
-A rapidly diminishing response and tolerance for Marinol can be developed suggesting there is an impact on sympathetic neurons. However, they don’t occur to the appetite stimulant effects.
-Tachycardia and conjunctival injections can occur due to dronabinol-induced sympathomimetic activity where orthostatic hypotension is experienced. There is an inconsistent effect on blood pressure.
Therapeutic effects:
Marinol is a pharmaceutical product used for several therapeutic reasons. It can be used as an appetite stimulant used for patients dealing with anorexia or severe weight loss during HIV/AIDS. It is also used to treat individuals for nausea and vomiting caused by chemotherapy. This is only taken when previous medical attempts in palliating these symptoms were not successful. Furthermore, Marinol has also been found to reduce cannabis withdrawal symptoms.
Side effects:
There are many side effects to using Marinol. These can vary from common to serious and abnormal.
Common side effects will include:
Mood changes
Dizziness
Anxiety
Headaches
Stomach/ Abdominal pain
Lack of coordination
Vomiting
Fatigue
Insomnia
However, more severe side effects can occur when using Marinol including:
Rapid heart rate
Fainting
Seizures
Hallucinations
This will require immediate attention from a medical expert.
Marinols synthetically formed properties show a unique mechanism of action that specifically minister to appetite stimulation and antiemetic properties. A large percentage of this drug is absorbed, yet an insignificant amount is able to enter the systemic circulation. This means the dosage given is crucial as first pass effects must be considered. Marinols are effective last resort drugs as they do contain a wide range of side effects and thus must be handled with precaution.
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