Marinol is the trade name given the artificially synthesized delta-9-tetrahydrocannabinol (THC) molecule. (In Europe, THC is marketed under the name Nabilone.) Marinol is marketed by Roxane Laboratories under a licensing agreement with Unimed Pharmaceuticals. Marinol is not marijuana. It is single molecule THC that does not contain any of the other cannabinoids found in herbal Cannabis. Marinol is manufactured in a sesame seed oil base and, like herbal Cannabis, is insoluble in water. 1
The lipid soluble nature of Cannabis and Marinol allow it to pass through the blood-brain barrier. (The blood-brain barrier is a cellular membrane that protects the brain and central nervous system from infection by filtering out certain chemical compounds.) This accounts for some of the cognitive effects of Cannabis and THC. Marinol also contains extra chemicals like gelatin, glycerin, methylparaben, propylpara-ben, yellow, red and blue dye, and titanium dioxide. (Vegetarians should be aware that gelatin is an animal product.) Any patient who has an allergy towards any of these substances should avoid taking Marinol.
The dosage of Marinol varies depending on set, setting, and medical condition. Generally a psychoactive dose is 0.05mg/kg. This translates into around 3.5 mg for a 70-kg (144-lb.) person. Patients should differentiate a psychoactive dose from a therapeutic dose. They are often not the same. Marinol is taken only by the oral route, unlike smoked Cannabis. Marinol is metabolized by the liver much the same way as Cannabis brownies are. Ninety percent (90%) of the Marinol dose is absorbed in the GI tract because of its high lipid solubility. Also, blood circulating through the intestines goes directly to the liver via the Portal veins carrying with it the large dose of THC absorbed through the stomach and intestines. Only about 10-20% of the dose reaches systemic circulation because the liver rapidly metabolizes the dose, converting it into other chemical compounds. 2
Marinol comes in three dosage forms: 2.5, 5 and 10 mg. It is approved by the Food and Drug Administration (FDA) for appetite stimulation in AIDS wasting syndrome, and nausea and vomiting in cancer chemotherapy, for patients who have not responded to more conventional treatments.
For anti-emetic use the usual dosage is 5 mg., three or four times per day, increasing the dosage carefully until the therapeutic benefit is obtained without serious side effects. This may be achieved by dividing doses in the morning and evening. Doses can also be given before or after meals. The important consideration is to achieve a stable blood level of the drug. Ten and fifteen milligram (mg.) doses are more psychoactive and do not increase the benefit.
For appetite stimulation Marinol is given in lower doses, usually around 5 milligrams per day. The dosage should be slowly titrated up to the effective dosage short of significant side effects. For naive users this process may take repeated trials of different doses at different times. Altering the dosage up or down should be done in consultation with the patient's medication prescriber. Patients should consider increasing the frequency of smaller doses before increasing the total dosage.
Side effects with Marinol vary widely among different people. One person's experience will be different than another's. Psychoactive effects may be desirable or undesirable. Roxane Laboratories lists euphoria (feeling "high") as an "adverse reaction," but this is often not the case. One of the significant psychiatric uses of Cannabis, if not Marinol, is as an anti-anxiety agent. However, other potentially serious side effects and adverse reactions may occur. The most common effects are: heart palpitations, tachycardia (rapid sustained heart rate), postural hypotension (low blood pressure caused by standing up), conjunctivitis (eye irritation), abdominal pain, nausea, vomiting, diarrhea, anxiety, confusion, depersonalization, paranoid reactions (possibly worse among people suffering from schizophrenia), and somnolence (lethargy). Less-common effects include tinnitus (ringing in the ears), depression, nightmares, visual disturbances, sweating and chills.
If disturbing experiences occur, patients should evaluate the benefits derived from the use of the drug versus the disagreeable effects. This risk-benefit ratio is the same for all drugs; Marinol and Cannabis are no exception. If the problems associated with the use of any drug exceed the benefits derived, patients should consider stopping therapy. Again, this is a decision that should be made with the knowledge of the prescriber.
The therapeutic benefits and side effects of dronabinol are reversible, that is, the effects fade away after the Marinol is stopped. Since Marinol and Cannabis are fat-soluble this process takes time as the drug slowly moves out of the tissues. Missed doses are not a problem. Taking the next dose early, then following the previous schedule will minimize drops in the blood level of the drug.
Marinol is metabolized by the liver much the same way as Cannabis brownies are.
...only 10-20% of the dose reaches systemic circulation because the liver rapidly metabolizes the dose, converting it into other chemical compounds.
Marinol...is approved by the FDA for appetite stimulation in AIDS wasting syndrome, and nausea and vomiting in cancer chemotherapy, for patients who have not responded to more conventional treatments.
Roxane Laboratories lists euphoria (feeling fine) as an "adverse reaction," but this is often not the case.
...the most common effects [of Marinol] are: heart palpitations, tachycardia, postural hypotension, conjunctivitis, abdominal pain, nausea, vomiting, diarrhea, anxiety, confusion, depersonalization, paranoid reactions, and somnolence.
If disturbing experiences occur, patients should evaluate the benefits derived from the use of the drug versus the disagreable effects.
As with Cannabis, there are few truly life-threatening reactions with Marinol. The most likely severe reaction is dysphoria or increased apprehension and fear without cause.
.combinations [of drugs] can be additive as one drug potentiates or increases the effects of another.
As with Cannabis, there are few truly life-threatening reactions with Marinol. The most likely severe reaction is dysphoria or increased apprehension and fear without cause. (Euphoria is the more common effect, a feeling of expansion and inner peace.) Persons suffering from severe liver or cardiac disease should use Marinol carefully. As is the case with Cannabis, the dosage-related mortality is extremely low. Simply put, there are no dosage-related deaths from using Marinol (or Cannabis) in medical literature.
Cannabis dependence syndrome is a psychiatric disease classification. Long-term heavy use of Cannabis can lead to a lack of ability to control use despite adverse consequences. Cannabis dependence syndrome is treated by abstinence.
Drug interactions can be either metabolic or pharmacological. Drugs interact because they share the same metabolic (chemical breakdown) pathways, or directly interact with each other chemically. The chemical interaction of drugs can create totally different compounds in the body and can be dangerous. Also, these chemical combinations can be additive as one drug potentiates or increases the effects of another. Marinol is no exception. It has several notable drug/drug interactions, though none life-threatening. Since Cannabis is chemically similar to Marinol it is reasonable to consider the following drug interactions in connection with Cannabis. Any person taking other pharmaceuticals along with Marinol or Cannabis should research interactions and consult with the prescriber.
Phenothiazines are a class of major tranquilizers including Compazine (prochlorperazine) and Thorazine (chlorpromazine). Use of phenothiazines in combination with Marinol may cause synergistic effects. (Synergistic actions are those where the effects of different drugs taken together result in greater action than either drug alone.)
Sympathomimetic agents are drugs that stimulate the sympathetic nervous system resulting in increased blood pressure and heightened excitement. Examples of sympathomimetic drugs include amphetamines, cocaine, and epinephrine. Use of Marinol or Cannabis with these drugs may result in cardiotoxicity, increasing hypertension (blood pressure), and tachycardia (rapid heart rate.)
Anticholinergic agents are those that block or interfere with parasympathetic nerve impulses. Parasympathetic nerve fibers carry impulses that constrict the pupil, contract smooth muscle of gastrointestinal tract and slow heart rate, among other functions. Examples of anticholinergic medications include atropine, scopolamine and antihistamines. Marinol or Cannabis use with these drugs may cause additive effects, including rapid heart rate and drowsiness.
Tricyclic antidepressant agents are a chemical class of antidepressants that increase the amount of neurotransmitters in the brain by blocking the "reuptake" of the neurotransmitter at the synapse. Common examples of tricyclic antidepressants include Elavil (amitriptyline), Anafranil (clomipramine), Sinequan (doxepin) and Pamelor (nortriptyline.) Use of Marinol or Cannabis with these drugs may lead to additive effects, hypertension or drowsiness.
Benzodiazapines, barbiturates and opioids are drugs that depress or decrease central nervous system function resulting in somnolence, lethargy, drowsiness, constipation and slow heart rate among other effects. Examples include Ativan (lorazepam) Xanax (alprazolam), alcohol, Serax (oxazepam), Valium (diazepam), heroin, morphine and methadone. Marinol or Cannabis use with these drugs may result in additive effects including drowsiness, dizziness or hypotension (low blood pressure.) These drugs may also metabolize more slowly because of competition for the same metabolic pathways.
Theophyline is a drug used to relieve bronchial spasms in diseases like emphysema and asthma by relaxing "smooth muscle" in the airway and interfering with enzyme production. Cannabis or Marinol used concurrently with theophyline may increase the metabolism of the theophyline yielding unpredictable results.
The lethal dose of Marinol is 30 milligrams per kilogram (mg./ kg.) This translates into 2100 mg. in a 70 kg. (144 lb.) person. This is an exceedingly high dose and reflects the relatively non-lethal nature of Marinol. Cannabis has an unobtainable lethal dosage because it does not overwhelm vital functions. Anyone attempting to overdose on Cannabis would probably fall asleep first.
Treatment of a life-threatening Marinol overdose consists of gastric lavage, intravenous fluid administration, vasopressors to stabilize blood pressure and perhaps intravenous Valium. If the person is responsive, treatment includes close monitoring of blood pressure and heart rate, reassurance, a quiet peaceful environment and hydration.
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