By: Rev. Frank Paul Jones aka Apostle Paul Castellano D.B.A. Jesus Christ I AM about to unveil the greatest conspiracy of modern age. The pharmaceutical industry sole mission is to kill people. Under the order of the Illuminati, the German Reich or who we have come to know as the Nazi party and their goal is to cause people of color to suffer, sometimes slowly, but they do not want people to feel good. At the same time controlling the world’s healthcare system.
The conspiracy is behind marijuana believe it or not. Long ago the pharmaceutical industry discovered marijuana is a miracle drug, that would revolutionize medical science and thereby drastically reducing the cost of healthcare and therefore their power and influence over the world.The controlled substance act of 1970 was signed by President Richard Nixon. Giving the Attorney General the authority to create scheduling for drugs based on certain guidelines. However without any real evidence or any study, they made marijuana a schedule one drug, meaning it had no medial use, was basically poison to be kept out of Americans hands at all cost to protect our people.
Find Cure – Cure AIDS
The U.S. Attorney General today is Eric Holder a black man then and now it is under: Attorney General Loretta Lynch
Under: Title 21 United States Code (USC) Controlled Substances Act:
The Attorney General shall, before initiating proceedings under subsection (a) of this section to control a drug or other substance or to remove a drug or other substance entirely from the schedules, and after gathering the necessary data, request from the Secretary a scientific and medical evaluation, and his recommendations, as to whether such drug or other substance should be so controlled or removed as a controlled substance.
Factors determinative of control or removal from schedules
In making any finding under subsection (a) of this section or under subsection (b) of section 812 of this title, the Attorney General shall consider the following factors with respect to eachdrug or other substance proposed to be controlled or removed from the schedules:
(1) Its actual or relative potential for abuse.
(2) Scientific evidence of its pharmacological effect, if known.
(3) The state of current scientific knowledge regarding the drug or other substance.
(4) Its history and current pattern of abuse.
(5) The scope, duration, and significance of abuse.
(6) What, if any, risk there is to the public health.
(7) Its psychic or physiological dependence liability.
(8) Whether the substance is an immediate precursor of a substance already controlled under this subchapter.
Rev Sep 2004 MARINOL®
In 2004, a clinical research was done that was approved by the FDA, Therefore even though the DEA improperly scheduled marijuana as a schedule one drug in 1970 it was proven to be effective for the intent of the research to help people with AIDS and cancer eat, but also unintentional they discovered that its the best possible sedative they have available, it is non addictive and you cannot die from an extreme overdose.
The Drug Cartels work for the DEA, who works for Eric Holder and Eric Holder works for President Barack Obama. While the non profit is extorting Medicaid and Medicare? Eric Holder has raise the scheduling of marijuana based on this research to at least 4. Based on these facts, the Federal Government is going to have to release and/or overturn at least all non violent marijuana convictions since September 2004. The DEA must be dismantled and Eric Holder might have to take the fall to protect President Barack Obama. This conspiracy called the war on drugs and could reach the White House.
The Proof:
500012 Rev Sep 2004
MARINOL® 
DESCRIPTION
Dronabinol is a cannabinoid designated chemically as (6aR-trans)-6a,7,8,10a-tetrahydro-6,6,9- trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol. Dronabinol has the following empirical and structural formulas:
Dronabinol, the active ingredient in MARINOL®Capsules, is synthetic delta-9- tetrahydrocannabinol (delta-9-THC). Delta-9-tetrahydrocannabinolis also a naturally occurring component of Cannabis sativa L. (Marijuana).
Dronabinol is a light yellow resinousoil that is sticky at room temperature and hardens upon refrigeration. Dronabinol is insolublein water and is formulated in sesameoil. It has a pKa of 10.6 and an octanol-water partition coefficient: 6,000:1 at pH 7.
Capsules for oral administration: MARINOL®Capsules is suppliedas round, soft gelatin capsulescontaining either 2.5 mg, 5 mg, or 10 mg dronabinol. Each MARINOL® Capsuleis formulated with the followinginactive ingredients: FD&C Blue No. 1 (5 mg), FD&CRed No. 40 (5 mg), FD&C YellowNo. 6 (5 mg and 10 mg), gelatin, glycerin,methylparaben, propylparaben, sesame oil, and titaniumdioxide.
CLINICAL PHARMACOLOGY
Dronabinol is an orallyactive cannabinoid which,like other cannabinoids, has complexeffects on the central nervous system(CNS), including centralsympathomimetic activity. Cannabinoid receptors have been discovered in neural tissues. These receptors may play a role in mediatingthe effects of dronabinol and other cannabinoids.
Pharmacodynamics
Dronabinol-induced sympathomimetic activitymay result in tachycardia and/orconjunctival injection. Its effects on blood pressure are inconsistent, but occasional subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing.
Dronabinol also demonstrates reversible effectson appetite, mood,cognition, memory,and perception. These phenomenaappear to be dose-related, increasing in frequency with higher dosages,and subject to great interpatient variability.
After oral administration, dronabinol has an onset of action of approximately 0.5 to 1 hours and peak effectat 2 to 4 hours.Duration of actionfor psychoactive effectsis 4 to 6 hours,but the appetite stimulanteffect of dronabinol may continuefor 24 hours or longerafter administration.
Tachyphylaxis and tolerance developto some of the pharmacologic effects of dronabinol and other cannabinoids with chronic use, suggesting an indirect effecton sympathetic neurons. In a study of the pharmacodynamics of chronic dronabinol exposure, healthymale volunteers (N = 12) received210 mg/day dronabinol, administered orallyin divided doses, for 16 days. An initial tachycardia induced by dronabinol was replaced successively by normal sinus rhythmand then bradycardia. A decrease in supine blood pressure, made worse by standing, was also observed initially. These volunteers developed tolerance to the cardiovascular and subjective adverse CNS effects of dronabinol within12 days of treatmentinitiation.
Tachyphylaxis and tolerance do not, however,appear to developto the appetite stimulanteffect of MARINOL®Capsules. In studiesinvolving patients with Acquired ImmuneDeficiency Syndrome(AIDS), the appetitestimulant effect of MARINOL® Capsuleshas been sustainedfor up to five monthsin clinical trials,at dosages rangingfrom 2.5 mg/day to 20 mg/day.
Pharmacokinetics
Absorption and Distribution: MARINOL® (Dronabinol) Capsulesis almost completely absorbed (90 to 95%) after singleoral doses. Due to the combinedeffects of firstpass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches the systemiccirculation. Dronabinol has a large apparent volume of distribution, approximately 10 L/kg, because of its lipid solubility. The plasma protein bindingof dronabinol and its metabolites is approximately 97%.
The elimination phase of dronabinol can be described using a two compartment model with an initial(alpha) half-life of about 4 hours and a terminal(beta) half-life of 25 to 36 hours. Becauseof its large volume of distribution, dronabinol and its metabolites may be excreted at low levels for prolonged periods of time.
The pharmacokinetics of dronabinol after single doses (2.5, 5, and 10 mg) and multipledoses (2.5, 5, and 10 mg given twice a day; BID) have been studiedin healthy women and men.
Summary of Multiple-Dose Pharmacokinetic Parameters of Dronabinol in Healthy Volunteers (n=34; 20-45 years) under FastedConditions
|
Mean (SD) PK Parameter Values
|
|
BID
Dose
|
Cmax ng/mL
|
Median Tmax (range), hr
|
AUC(0-12)
ng•hr/mL
|
|
2.5 mg
|
1.32 (0.62)
|
1.00 (0.50-4.00)
|
2.88 (1.57)
|
|
5 mg
|
2.96 (1.81)
|
2.50 (0.50-4.00)
|
6.16 (1.85)
|
|
10 mg
|
7.88 (4.54)
|
1.50 (0.50-3.50)
|
15.2 (5.52)
|
A slight increase in dose proportionality on mean Cmax and AUC (0-12) of dronabinol was observed with increasing dose over the dose range studied.
Metabolism: Dronabinol undergoes extensivefirst-pass hepatic metabolism, primarily by microsomal hydroxylation, yielding both active and inactive metabolites. Dronabinol and its principalactive metabolite, 11-OH-delta-9-THC, are present in approximately equal concentrations in plasma.
Concentrations of both parent drug and metabolite peak at approximately 0.5 to 4 hours after oral dosingand decline over several days. Values for clearance averageabout 0.2 L/kg-hr,but are highlyvariable due to the complexity of cannabinoid distribution.
Elimination: Dronabinol and its biotransformation productsare excreted in both feces and urine.Biliary excretion is the major route of elimination with about half of a radio-labeled oral dose being recovered from the feceswithin 72 hours as contrasted with 10 to 15% recovered from urine. Less than 5% of an oral dose is recoveredunchanged in the feces.
Following singledose administration, low levels of dronabinol metabolites have been detectedfor more than 5 weeks in the urine and feces.
In a study of MARINOL® Capsulesinvolving AIDS patients, urinarycannabinoid/creatinine concentration ratios were studiedbi-weekly over a six week period.The urinary cannabinoid/creatinine ratio was closely correlated with dose. No increasein the cannabinoid/creatinine ratio was observed after the first two weeks of treatment, indicating that steady- state cannabinoid levelshad been reached.This conclusion is consistent with predictions based on the observed terminal half-life of dronabinol.
Special Populations: The pharmacokinetic profileof MARINOL® Capsules has not been investigated in either pediatric or geriatric patients.
Clinical Trials
Appetite Stimulation: The appetite stimulant effect of MARINOL®(Dronabinol) Capsules in the treatment of AIDS-related anorexiaassociated with weightloss was studiedin a randomized, double-blind, placebo-controlled studyinvolving 139 patients. The initial dosageof MARINOL® Capsulesin all patients was 5 mg/day,administered in doses of 2.5 mg one hour beforelunch and one hour beforesupper. In pilot studies, earlymorning administration of MARINOL® Capsulesappeared to have been associated with an increased frequency of adverse experiences, as comparedto dosing later in the day. The effectof MARINOL® Capsuleson appetite, weight,mood, and nausea was measuredat scheduled intervals during the six-weektreatment period. Side effects (feelinghigh, dizziness, confusion, somnolence) occurredin 13 of 72 patients(18%) at this dosage level and the dosagewas reduced to
2.5 mg/day, administered as a single dose at supper or bedtime.
As comparedto placebo, MARINOL® Capsulestreatment resultedin a statistically significant improvement in appetite as measuredby visual analogscale (see figure).Trends toward improved body weight and mood, and decreases in nausea were also seen.
After completing the 6-week study,patients were allowedto continue treatment with MARINOL®
Capsulesin an open-label study, in which there was a sustainedimprovement in appetite.
Antiemetic: MARINOL®(Dronabinol) Capsules treatment of chemotherapy-induced emesis was evaluated in 454 patients with cancer,who received a total of 750 coursesof treatment of various malignancies. The antiemetic efficacy of MARINOL®Capsules was greatest in patients receiving cytotoxic therapy with MOPP for Hodgkin’sand non-Hodgkin’s lymphomas. MARINOL®Capsules dosages ranged from 2.5 mg/day to 40 mg/day, administered in equally divideddoses every four to six hours (four times daily). As indicated in the followingtable, escalating the MARINOL® Capsulesdose above 7 mg/m2 increased the frequency of adverse experiences, with no additional antiemetic benefit.
MARINOL®Capsules Dose: ResponseFrequency and AdverseExperiences*
(N = 750 treatmentcourses)
|
MARINOL® Capsules Dose
<7 mg/m2
>7 mg/m2
|
Response Frequency (%)
|
Adverse Events Frequency (%)
|
|
Complete
|
Partial
|
Poor
|
None
|
Nondysphoric
|
Dysphoric
|
|
36
|
32
|
32
|
23
|
65
|
12
|
|
33
|
31
|
36
|
13
|
58
|
28
|
*Nondysphoric events consisted of drowsiness, tachycardia, etc.
Combination antiemetic therapy with MARINOL®Capsules and a phenothiazine (prochlorperazine) may resultin synergistic or additiveantiemetic effects and attenuatethe toxicities associated with each of the agents.
INDIVIDUALIZATION OF DOSAGES
The pharmacologic effectsof MARINOL® (Dronabinol) Capsulesare dose-related and subject to considerable interpatient variability. Therefore, dosage individualization is criticalin achieving the maximumbenefit of MARINOL®Capsules treatment.
Appetite Stimulation: In the clinicaltrials, the majorityof patients were treatedwith 5 mg/day MARINOL®Capsules, although the dosages rangedfrom 2.5 to 20 mg/day. For an adult:
· Begin with 2.5 mg beforelunch and 2.5 mg before supper.If CNS symptoms (feelinghigh, dizziness, confusion, somnolence) do occur, they usuallyresolve in 1 to 3 days with continued dosage.
· If CNS symptomsare severe or persistent, reducethe dose to 2.5 mg beforesupper. If symptoms continueto be a problem, taking the single dose in the evening or at bedtime may reducetheir severity.
· When adverseeffects are absentor minimal and further therapeutic effectis desired, increase the dose to 2.5 mg before lunch and 5 mg before supper or 5 and 5 mg. Although most patientsrespond to 2.5 mg twice daily, 10 mg twice daily has been toleratedin about half of the patients in appetite stimulation studies.The pharmacologic effectsof MARINOL® Capsulesare reversible upon treatmentcessation.
Antiemetic: Most patients respondto 5 mg three or four times daily. Dosagemay be escalated duringa chemotherapy cycle or at subsequent cycles, based upon initial results.Therapy should be initiated at the lowestrecommended dosage and titrated to clinical response. Administration of MARINOL® Capsuleswith phenothiazines, such as prochlorperazine, has resulted in improved efficacyas compared to either drug alone,without additional toxicity.
Pediatrics: MARINOL® Capsules is not recommended for AIDS-related anorexiain pediatric patientsbecause it has not been studied in this population. The pediatric dosagefor the treatment of chemotherapy-induced emesis is the same as in adults.Caution is recommended in prescribing MARINOL®Capsules for childrenbecause of the psychoactive effects.
Geriatrics: Caution is advisedin prescribing MARINOL® Capsulesin elderly patientsbecause they are generally more sensitive to the psychoactive effectsof drugs. In antiemetic studies, no difference in tolerance or efficacy was apparentin patients >55 years old.
INDICATIONS AND USAGE
MARINOL® (Dronabinol) Capsules is indicated for the treatmentof:
· anorexia associated with weight loss in patientswith AIDS; and
· nausea and vomitingassociated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
CONTRAINDICATIONS
MARINOL® (Dronabinol) Capsules is contraindicated in any patient who has a history of hypersensitivity to any cannabinoid or sesame oil.
WARNINGS
Patients receiving treatment with MARINOL®Capsules shouldbe specifically warnednot to drive, operatemachinery, or engage in any hazardous activity until it is established that they are able to toleratethe drug and to performsuch tasks safely.
PRECAUTIONS
General: The risk/benefit ratio of MARINOL® (Dronabinol) Capsulesuse should be carefully evaluated in patientswith the following medical conditions becauseof individual variation in response and toleranceto the effects of MARINOL® Capsules.
MARINOL® Capsulesshould be used with caution in patientswith cardiac disorders becauseof occasional hypotension, possible hypertension, syncope, or tachycardia (see CLINICAL PHARMACOLOGY).
MARINOL® Capsulesshould be used with cautionin patients with a historyof substance abuse, including alcoholabuse or dependence, becausethey may be more prone to abuse MARINOL®Capsules as well. Multiple substanceabuse is common and marijuana, which contains the same active compound, is a frequently abused substance.
MARINOL® Capsulesshould be used with cautionand careful psychiatric monitoring in patients with mania,depression, or schizophrenia because MARINOL® Capsulesmay exacerbate these illnesses.
MARINOL® Capsulesshould be used with cautionin patients receiving concomitant therapywith sedatives, hypnotics or otherpsychoactive drugs becauseof the potential for additiveor synergistic CNS effects.
MARINOL® Capsulesshould be used with cautionin pregnant patients, nursing mothers,or pediatric patients because it has not been studiedin these patientpopulations.
Information for Patients: Patients receiving treatment with MARINOL® (Dronabinol) Capsules should be alerted to the potentialfor additive centralnervous system depression if MARINOL® Capsulesis used concomitantly with alcohol or other CNS depressants such as benzodiazepines and barbiturates.
Patients receiving treatment with MARINOL® Capsulesshould be specifically warned not to drive,operate machinery, or engage in any hazardous activityuntil it is established that they are able to toleratethe drug and to performsuch tasks safely.
Patients using MARINOL® Capsulesshould be advisedof possible changesin mood and otheradverse behavioral effects of the drug so as to avoid panicin the event of such manifestations. Patients should remain under the supervision of a responsible adult during initialuse of MARINOL® Capsules and following dosageadjustments.
Drug Interactions: In studiesinvolving patients with AIDS and/or cancer, MARINOL®(Dronabinol) Capsules has been co-administered with a variety of medications (e.g., cytotoxic agents,anti-infective agents,sedatives, or opioid analgesics) without resulting in any clinically significant drug/drug interactions. Although no drug/drug interactions were discovered duringthe clinical trials of MARINOL®Capsules, cannabinoids may interactwith other medications throughboth metabolic and pharmacodynamic mechanisms. Dronabinol is highly proteinbound to plasma proteins,and therefore, might displaceother protein-bound drugs. Although this displacement has not been confirmedin vivo, practitioners should monitorpatients for a changein dosage requirements when administering dronabinol to patientsreceiving other highlyprotein-bound drugs.Published reports of drug/drug interactions involving cannabinoids are summarized in the followingtable.
|
CONCOMITANT DRUG
|
CLINICAL EFFECT(S)
|
|
Amphetamines, cocaine, other sympathomimetic agents
|
Additive hypertension, tachycardia, possibly cardiotoxicity
|
|
Atropine, scopolamine, antihistamines, other anticholinergic agents
|
Additive or super-additive tachycardia, drowsiness
|
|
Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants
|
Additive tachycardia, hypertension, drowsiness
|
|
Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants
|
Additive drowsiness and CNS depression
|
|
Disulfiram
|
A reversible hypomanic reaction was reported in a 28 y/o man who smoked marijuana; confirmed by dechallenge and rechallenge
|
|
Fluoxetine
|
A 21 y/o female with depression and bulimia receiving 20 mg/day fluoxetine X 4 wks became hypomanic after smoking marijuana; symptoms resolved after 4 days
|
|
Antipyrine, barbiturates
|
Decreased clearance of these agents, presumably via competitive inhibition of metabolism
|
|
Theophylline
|
Increased theophylline metabolism reported with smoking of marijuana; effect similar to that following smoking tobacco
|
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies in mice and rats have been conducted under the US National Toxicology Program (NTP). In the 2-yearcarcinogenicity study in rats,there was no evidence of carcinogenicity at doses up to 50 mg/kg/day, about 20 times the maximumrecommended human dose on a body surface area basis. In the 2-yearcarcinogenicity study in mice, treatmentwith dronabinol at 125 mg/kg/day, about 25 times the maximumrecommended human dose on a body surface area basis, producedthyroid follicular cell adenomain both male and femalemice but not at 250 or 500 mg/kg/day.
Dronabinol was not genotoxic in the Ames tests,the in vitro chromosomal aberration test in Chinese hamster ovary cells, and the in vivo mouse micronucleus test. It, however,produced a weak positive response in a sister chromatid exchangetest in Chinese hamster ovary cells.
In a long-term study (77 days) in rats, oral administration of dronabinol at doses of 30 to 150 mg/m2, equivalent to 0.3 to 1.5 times maximum recommended human dose (MRHD) of 90 mg/m2/day in cancer patients or 2 to 10 times MRHD of 15 mg/m2/day in AIDS patients, reducedventral prostate, seminal vesicleand epididymal weights and caused a decreasein seminal fluid volume.Decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testis were also observed. However, sperm count, mating successand testosterone levelswere not affected.The significance of these animal findingsin humans is not known.
Pregnancy: Pregnancy Category C. Reproduction studieswith dronabinol have been performedin mice at 15 to 450 mg/m2, equivalent to 0.2 to 5 times maximumrecommended human dose (MRHD)
of 90 mg/m2/day in cancer patients or 1 to 30 times MRHD of 15 mg/m2/day in AIDS patients,and in rats at 74 to 295 mg/m2 (equivalent to 0.8 to 3 times MRHD of 90 mg/m2 in cancer patients or 5 to 20 times MRHD of 15 mg/m2/day in AIDS patients). These studieshave revealed no evidenceof teratogenicity due to dronabinol. At these dosages in mice and rats, dronabinol decreasedmaternal weightgain and number of viable pups and increasedfetal mortality and early resorptions. Such effects were dose dependentand less apparentat lower doseswhich produced less maternaltoxicity. There are no adequateand well-controlled studies in pregnant women. Dronabinol should be used only if the potential benefit justifies the potentialrisk to the fetus.
Nursing Mothers:Use of MARINOL® Capsulesis not recommended in nursing motherssince, in additionto the secretion of HIV virus in breast milk, dronabinol is concentrated in and secretedin human breast milk and is absorbedby the nursing baby.
Geriatric Use: Clinical studiesof MARINOL® (Dronabinol) Capsulesin AIDS and cancer patientsdid not include the sufficient numbers of subjects aged 65 and over to determinewhether they responddifferently from youngersubjects. Other reportedclinical experience has not identified differences in responses between the elderlyand younger patients. In general, dose selection for an elderlypatient should be cautioususually starting at the low end of the dosingrange, reflecting the greater frequencyof decreased hepatic,renal, or cardiacfunction, increased sensitivity to psychoactive effects and of concomitant diseaseor other drug therapy.
ADVERSE REACTIONS
Adverse experiences information summarized in the tables below was derived from well-controlled clinical trials conducted in the USand US territories involving 474 patients exposedto MARINOL® (Dronabinol) Capsules.Studies of AIDS-related weight loss included157 patients receivingdronabinol at a dose of 2.5 mg twice daily and 67 receiving placebo. Studies of different durations were combined by considering the first occurrence of events duringthe first 28 days.Studies of nausea andvomiting relatedto cancer chemotherapy included317 patients receiving dronabinol and 68 receiving placebo.
A cannabinoid dose-related “high” (easylaughing, elation and heightened awareness) has been reportedby patients receiving MARINOL® Capsules in both the antiemetic (24%) and the lower dose appetitestimulant clinicaltrials (8%) (see Clinical Trials).
The most frequently reported adverse experiences in patients with AIDS during placebo-controlled clinicaltrials involved the CNS and were reportedby 33% of patients receivingMARINOL® Capsules. About 25% of patientsreported a minor CNS adverse event during the first 2 weeks and about 4% reported such an event each week for the next 6 weeks thereafter.
PROBABLY CAUSALLYRELATED: Incidence greaterthan 1%.
Rates derivedfrom clinical trialsin AIDS-related anorexia(N=157) and chemotherapy-related nausea(N=317). Rates were generally higher in the anti-emetic use (given in parentheses).
Body as a whole:Asthenia.
Cardiovascular: Palpitations, tachycardia, vasodilation/facial flush.
Digestive: Abdominal pain*, nausea*, vomiting*.
Nervous system:(Amnesia), anxiety/nervousness, (ataxia), confusion, depersonalization, dizziness*, euphoria*, (hallucination), paranoidreaction*, somnolence*, thinking abnormal*.
*Incidence of events 3% to 10%
PROBABLY CAUSALLYRELATED: Incidence less than 1%.
Event rates derivedfrom clinical trialsin AIDS-related anorexia(N=157) and chemotherapy-related nausea(N=317).
Cardiovascular: Conjunctivitis*,hypotension*.
Digestive: Diarrhea*, fecal incontinence.
Musculoskeletal: Myalgias.
Nervous system:Depression, nightmares, speech difficulties, tinnitus.
Skin and Appendages: Flushing*.
Special senses:Vision difficulties.
*Incidence of events0.3% to 1%
CAUSAL RELATIONSHIP UNKNOWN: Incidence less than 1%.
The clinical significance of the association of these events with MARINOL® Capsulestreatment is unknown, but they are reported as alertinginformation for the clinician.
Body as a whole:Chills, headache, malaise. Digestive: Anorexia, hepaticenzyme elevation. Respiratory: Cough, rhinitis, sinusitis.
Skin and Appendages: Sweating.
DRUG ABUSE AND DEPENDENCE
MARINOL® (Dronabinol) Capsules is one of the psychoactive compounds presentin cannabis, and is abusableand controlled [Schedule III (CIII)] under the Controlled Substances Act. Both psychological and physiological dependence have been notedin healthy individuals receiving dronabinol, but addiction is uncommon and has only been seen after prolongedhigh dose administration.
Chronic abuse of cannabishas been associated with decrements in motivation, cognition, judgement, and perception. The etiologyof these impairments is unknown,but may be associated with the complex processof addiction rather than an isolatedeffect of the drug. No such decrements in psychological, socialor neurological status have been associated with the administration of MARINOL® Capsulesfor therapeutic purposes.
In an open-label study in patientswith AIDS who receivedMARINOL® Capsules for up to five months,no abuse, diversion or systematic change in personality or social functioning were observed despitethe inclusion of a substantial number of patients with a past history of drug abuse.
An abstinence syndrome has been reportedafter the abruptdiscontinuation of dronabinol in volunteers receiving dosagesof 210 mg/day for 12 to 16 consecutive days. Within 12 hoursafter discontinuation, these volunteers manifested symptoms such as irritability, insomnia, and restlessness. By approximately 24 hours post-dronabinol discontinuation, withdrawal symptoms intensified to include “hot flashes”, sweating, rhinorrhea, loose stools, hiccoughsand anorexia.
These withdrawal symptoms graduallydissipated over the next 48 hours. Electroencephalographic changesconsistent with the effects of drug withdrawal (hyperexcitation) were recordedin patients after abrupt dechallenge. Patientsalso complained of disturbedsleep for severalweeks after discontinuing therapy with high dosages of dronabinol.
OVERDOSAGE
Signs and symptomsfollowing MILD MARINOL®(Dronabinol) Capsules intoxication include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddenedconjunctiva, dry mouth and tachycardia; following MODERATE intoxication include memory impairment, depersonalization, mood alteration, urinaryretention, and reduced bowel motility; and following SEVEREintoxication include decreasedmotor coordination, lethargy, slurredspeech, and posturalhypotension. Apprehensive patientsmay experience panic reactions and seizures may occur in patientswith existing seizuredisorders.
The estimated lethalhuman dose of intravenous dronabinol is 30 mg/kg (2100 mg/ 70 kg).
Significant CNS symptoms in antiemetic studies followedoral doses of 0.4 mg/kg (28 mg/70 kg) of MARINOL® Capsules.
Management: A potentially seriousoral ingestion, if recent,should be managed with gut decontamination. In unconscious patientswith a secure airway, instillactivated charcoal(30 to 100 g in adults, 1 to 2 g/kg in infants) via a nasogastric tube. A salinecathartic or sorbitol may be added to the first dose of activated charcoal.Patients experiencing depressive, hallucinatory or psychoticreactions shouldbe placed in a quiet area and offeredreassurance. Benzodiazepines (5 to 10 mg diazepam po) may be used for treatment of extremeagitation. Hypotension usuallyresponds to Trendelenburg position and IV fluids. Pressorsare rarely required.
DOSAGE AND ADMINISTRATION
Appetite Stimulation: Initially, 2.5 mg MARINOL®(Dronabinol) Capsulesshould be administered orallytwice daily (b.i.d.),before lunch and supper. For patients unable to toleratethis 5 mg/day dosage of MARINOL®Capsules, the dosage can be reducedto 2.5 mg/day, administered as a single dose in the evening or at bedtime.If clinically indicated and in the absence of significant adverseeffects, the dosage may be gradually increased to a maximumof 20 mg/day MARINOL®Capsules, administered in divided oral doses. Cautionshould be exercised in escalating the dosageof MARINOL® Capsulesbecause of the increased frequencyof dose-related adverse experiences at higher dosages(see PRECAUTIONS).
Antiemetic: MARINOL®Capsules is best administered at an initial dose of 5 mg/m2, given 1 to 3 hours prior to the administration of chemotherapy, then every2 to 4 hours after chemotherapy is given, for a total of 4 to 6 doses/day. Should the 5 mg/m2 dose prove to be ineffective, and in the absenceof significant side effects, the dose may be escalated by 2.5 mg/m2 increments to a maximum of 15 mg/m2 per dose. Caution should be exercised in dose escalation, however, as the incidence of disturbing psychiatric symptoms increases significantly at maximumdose (see PRECAUTIONS).
STORAGE CONDITIONS
MARINOL® (Dronabinol) Capsules should be packaged in a well-closed container and stored in a cool environment between 8° and 15°C (46° and 59°F) and alternatively could be stored in a refrigerator. Protect from freezing.
HOW SUPPLIED
MARINOL® Capsules(dronabinol solution in sesame oil in soft gelatin capsules)
2.5 mg white capsules (Identified UM or RL).
NDC 0051-0021-21 (Bottle of 60 capsules).
5 mg dark brown capsules (Identified UM or RL).
NDC 0051-0022-11 (Bottle of 25 capsules).
10 mg orange capsules(Identified UM or RL).
NDC 0051-0023-21 (Bottle of 60 capsules).
MARINOL® is a registered trademark of Unimed Pharmaceuticals, Inc. and is Manufactured by Banner Pharmacaps, Inc.
High Point, NC 27265 500012Rev Sep 2004
© 2004 Solvay Pharmaceuticals, Inc.
A Solvay Pharmaceuticals, Inc. Company Marietta, GA 30062
Rev. Frank Paul Jones aka Apostle Paul Castellano D.B.A. Jesus Christ
DBAJesusChrist.org 