Marijuana

Indications

The major medical indications of marijuana are to relieve symptoms rather than cure disease. Medical marijuana is not approved by the US Food and Drug Administration (FDA) to treat any medical condition. However, it has been studied to be beneficial in several conditions. TCH has been shown to decrease intraocular pressure, yet no major ophthalmology organizations support medical cannabis use for glaucoma at this time. In some studies, approximately 50% of patients with MS and spinal cord injuries seem to have improvement in muscle spasms. The use of cannabis and cannabinoids for chronic pain is controversial, but it is commonly used for this purpose. Other medical conditions that marijuana is used to treat include neuropathic pain, spasticity related to Parkinson’s disease, seizures, nausea and vomiting related to chemotherapy, anxiety disorder, sleep disorder, Tourette syndrome, and Crohn’s disease. Furthermore, it increases appetite in AIDS or AIDS-related wasting, and psychiatric disorders such as posttraumatic stress disorder.

Mechanism of Action

Marijuana is a complex of more than 400 compounds, including flavonoids, terpenoids, and cannabinoids. Cannabinoids are the active ingredients and appear to have individual interactive effects that contribute to the net effect of marijuana. Cannabinoids are metabolized by p450 enzymes in the liver.   The principal cannabinoid is tetrahydrocannabinol (THC), which is responsible for both the psychoactive effects sought by recreational users and the therapeutic effects of the drug. Although the mechanism of action is still being researched, it is known that there are widespread cannabinoid receptors in the brain and peripheral tissues known as the endocannabinoid system. The endocannabinoid system regulates metabolism, appetite, blood pressure, glycemic control, immune response, and sense of reward. Although the receptors are located throughout the body, the most prominent effects arise from interactions in the central nervous system. Since it has a high lipid-soluble profile, it circulates through the body easily and causes a variety of effects based on the receptors and dosage.

Administration

Marijuana can be administered in many different ways – orally, sublingually, or topically. It can also be smoked, mixed into foods, and brewed as a tea. Typically cannabis is smoked, which has the advantage of rapid onset and easy titration, as well as allows it to be delivered to the brain and circulation rapidly.  Smoked cannabis has had difficulty being approved for medical use for multiple reasons, an important one being the variable mixture of THC, other cannabinoids, carcinogens and other toxic substances to the lungs.  When ingested orally, the pharmacokinetics vary greatly, and the onset of action is delayed with maximum blood levels being reached up to six hours post ingestion and with a half-life of up to 20-30 hours. The topical route, such as making it into a liniment, has been used for arthritic pain with varying success. Routes such as lozenges, sublingual tablets, skin patches, or suppositories have been attempted for medical purposes but have had difficulty obtaining standardized effects.  The combinations of cannabinoids in each preparation can vary substantially, which makes precise dosing difficult.

Adverse Effects

The most common emergency caused by marijuana ingestion is a panic attack.  Other common adverse effects include dizziness, dry mouth, nausea, disorientation, euphoria, confusion, sedation, increase heart rate, and breathing problems. Approximately one in 10 adult users of marijuana develops an addiction, with higher rates reported in adolescents. It also has been shown to increase the risk of psychotic disorders, as well as exacerbate or relapse symptoms in those with psychotic disorders.  Some studies suggest that there is an increased risk of lung cancer from inhalation of marijuana as well as an association between inhalational marijuana and spontaneous pneumothorax.  It is also linked to complications in bullous emphysema and COPD, such as increased wheezing, cough, and phlegm production. Long-term use has also been associated with periodontal disease, pre-term birth if used at 20 weeks gestation, and more frequent pain crisis in sickle cell patients.  Chronic use has also been well documented as a cause of cannabinoid hyperemesis syndrome (CHS), which was first described in Australia by Allen et al in 2004.  This syndrome is characterized by recurrent episodes of nausea and vomiting relieved by hot showers.
Studies have shown that adolescents who used marijuana were significantly less likely than their non-using peers to finish high school or obtain a degree, and were more likely to develop dependence, use other drugs or attempt suicide.  Marijuana has also been shown to worsen some cases of depression, anxiety disorders, and pre-existing schizophrenia.  Marijuana use has also been linked to acute reversible psychotic reactions as well as 24% of new psychosis cases in adolescents.
There have also been complications linked to the abrupt cessation of marijuana after chronic use.  Cannabis withdrawal typically requires no treatment. Symptoms may include irritability, poor sleep, poor appetite, and restlessness.

Contraindications

There is minimal information available about contraindications with cannabis-derived pharmaceuticals and medical cannabis. Known contraindications to dronabinol, a synthetic THC and DEA schedule 3 drug, include hypersensitivity to the drug, allergy to cannabinoids/propylene glycol/peppermint oil, as well as concomitant use of ritonavir, which may lead to potential toxicity. Medical contraindications are cardiovascular disease, arrhythmias, poorly controlled hypertension, severe heart failure, history of psychotic disorder, patients under eight years old, pregnant women, or nursing women.  One study showed that marijuana can worsen preexisting heart disease, resulting in up to a five-fold increase in heart attacks one hour after smoking marijuana.

Monitoring

Marijuana use can be detected up to 2–5 days after exposure for infrequent users and up to 1-15 days for chronic or heavy users.  Those with high body fat may have positive tests from 1 to 30 days.  The actual detection times vary based on many factors including the method of use, metabolism, and volume of distribution.  It also depends on the type of THC metabolite being tested for.   False positives have been known to be triggered by several medications and materials, although more detailed and expensive tests are able to differentiate further if necessary.

Toxicity

Marijuana is classified as a Schedule I substance by the FDA, and therefore is not accepted for medical use and has a high abuse potential from a federal point of view. As a result, doctors cannot prescribe marijuana, but in states that allow its use to treat medical conditions, doctors may be able to certify its use.  Both dronabinol (synthetic THC) and nabilone (a synthetic cannabinoid receptor antagonist) are individual oral agents registered for use in the US available commercially but have been difficult to titrate to receive therapeutic effects.   As of now, it is not known to what extent a physician who certifies a patient for medical marijuana is liable for negative outcomes, or whether medical insurance will cover liability.

Questions

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References

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