Marijuana (Herb/Suppl)

Decrease intraocular pressure, analgesia, antiemetic effects, appetite stimulant

Availability

The United States (US) Drug Enforcement Administration (DEA) classifies marijuana as a Schedule 1 substance under the Controlled Substances Act (CSA). Schedule I drugs are recognized as having a high potential for abuse with insufficient evidence for safety and efficacy with no currently accepted medical use for treatment in the US

Marijuana is not approved by the US Food and Drug Administration (FDA) for medical use in the US and remains classified as an illicit drug by the DEA. However, several states have adopted individual State Medical Marijuana Laws including: Alaska, California, Colorado, Hawaii, Maine, Maryland, Michigan, Montana, Nevada, New Mexico, Oregon, Rhode Island, Washington, and Vermont

In October of 2009 the US Justice Department announced that it will no longer enforce federal drug laws on persons who use marijuana for medicinal purposes or their sanctioned suppliers, as long as state laws are followed

Frequency Not Defined

Tolerance

Psychological or physical dependence

Withdrawal symptoms

Altered sensorium

Dizziness

Somnolence

Fatigue

Reduced coordination

Cognitive impairment

Impaired balance

Euphoria

Paranoia

Hallucinations

Mood alterations

Panic

Anxiety

Hypotension

Hypertension

Tachycardia

Flushing

Syncope

Xerostomia

Nausea

Vomiting

Dysgeusia

Tooth discoloration

Anorexia

Increased appetite

Oral candidiasis

Diarrhea

Constipation

Urinary retention

Skin rash

Dry eyes

Blurred vision

Allergy

Cough

Pharyngitis

Contraindications

Hypersensitivity

Coadministration with dronabinol (Cannabis derivative)

Cautions

History of substance abuse or mental illness

Hepatic disease

Cardiovascular disease

Seizure disorders

Nonpharmaceutical preparations contaminated with the fungus which may be hazardous to patients with compromised immune systems

Geriatric patients

Operating machinery or driving

Drug interactions

• May potenitate CNS depression w/ concomitant use with CNS depressants (eg, barbiturates, ethanol, anxiolytics, sedatives, and hypnotics, sedating H1-blockers, SSRIs, TCAs)
• Use of marijuana with sedating anticholinergics may result in additive tachycardia and drowsiness
• Other: cocaine, disulfiram, ethanol, protease inhibitors, sildenafil, theophylline, cyclophosphamide, doxorubicin
• Cannabidiol, an inactive constituent of cannabis, may weakly inhibit cytochrome P450 enzymes (CYP1A2, 2C19, 2D6, & 3A4)
• Cannabis is also a minor substrate for CYP2C9, 2C19, 2D6, 3A4

Pregnancy

FDA pregnancy category not available; insufficient data regarding safety to fetus, avoid use

Case-control study reported maternal use and childhood acute nonlymphoblastic leukemia (ANLL); Children’s Cancer Study Group report 10-fold increase of ANLL w/ maternal use (Robison et al, 1989; Briggs, 1998)

Some sources found increased risk for low birth weight w/ maternal use

Lactation

THC found in Marijuana is reported to be concentrated and secreted into breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Tetrahydrocannabinol (THC), a component of marijuana, acts both centrally and peripherally on endogenous cannabinoid receptors; activation of cannabinoid receptors affects serotonin release, increases catecholamines, inhibits parasympathetic activity, and inhibits prostaglandin biosynthesis

Pharmacokinetics

Absorption: 10-20% (inhaled); 1-10% (PO)

Onset of action: 6-12 min (inhaled); 30-120 min (PO)

Peak effect: 20-30 min (inhaled); 2-3 hrs (PO)

Toxic dose (THC): 15 mg/kg; Lethal dose: 30 mg/kg

Duration of effect: 2-6 hrs

Vd: 10 L/kg (increases with chronic use)

Protein Bound: 97-99%

Metabolism: Hepatic hydroxylation to active and inactive metabolites, then further metabolized by alcohol dehydrogenase or alternatively, metabolites can be further oxidized to more polar compounds and glucuronide conjugates

Excretion: Feces 30-50%; 10-16% excreted in the urine as metabolites

Half-life: 28 hr (56 hr chronic use)