MEDICALMARIJUANA The Highs and Lows of Medical Marijuana Jill Vargo Cavalet, MHS, PA-C Marijuana use is prevalent worldwide yet remains controversial in health care. The general public often regards marijuana as a benign substance, but clear risks are associated with its use. Given the legalization of medical marijuana in more than 20 states, clinicians need to be aware of its negative effects—and its potential therapeutic benefits. arijuana has been used medicinally world- use. Use of marijuana for medical purposes requires wide for thousands of years.1,2 In the early a careful examination of the risks and benefits. M1990s, the discovery of cannabinoid re- ceptors in the central and peripheral nervous sys- PHARMACOKINETICS tems began to propagate interest in other potential Marijuana contains approximately 60 cannabinoids, therapeutic values of marijuana.3 Since then, mari- two of which have been specifically identified as pri- juana has been used by patients experiencing che- mary components. The first, delta-9 tetrahydrocan- motherapy-induced anorexia, nausea and vomiting, nabinol (THC), is believed to be the most psychoac- pain, and forms of spasticity. Use among patients tive.4,5 THC was identified in 1964 and is responsible with glaucoma and HIV/AIDS has also been widely for the well-documented symptoms of euphoria, reported. appetite stimulation, impaired memory and cogni- In light of this—and of increasing efforts to legal- tion, and analgesia. The THC content in marijuana ize medical marijuana use across the United States— products varies widely and has increased over time, clinicians should be cognizant of the substance’s complicating research on the long-term effects of negative effects, as well as its potential health ben- marijuana use.5,6 efits. Marijuana has significant systemic effects and The second compound, cannabidiol (CBD), is a associated risks of which patients and health care serotonin receptor agonist that lacks psychoactive providers should be aware. Questions remain re- effects. Potential benefits of CBD include antiemetic garding the safety, efficacy, and long-term impact of and anxiolytic properties, as well as anti-inflamma- tory effects. There is some evidence to suggest that CBD might also have antipsychotic properties.1,4 QUICK SUMMARY Recommendations for Marijuana Use AVAILABLE FORMULATIONS Two synthetic forms of THC have been approved Evidence for by the FDA since 1985 for medicinal use: nabilone Chemotherapy-associated nausea/vomiting (categorized as a Schedule II drug) and dronabinol Glaucoma (Schedule III). Both are cannabinoid receptor ago- Multiple sclerosis spasticity and/or pain nists approved for treating chemotherapy-induced nausea and vomiting. They are recommended for use No current evidence for after failure of standard therapies, such as 5-HT3 re- Alzheimer disease Parkinson disease ceptor antagonists, but overall interest has decreased Chron disease Rheumatoid arthritis since the advent of agents such as ondansetron.2,4 Chronic pain Seizures HIV/AIDS Tourette syndrome Jill Vargo Cavalet is a Clinical Associate Professor in the Depart- Huntington disease ment of PA Sciences at Saint Francis University in Loretto, PA, and practices clinically in inpatient psychiatry. 40 Clinician Reviews • OCTOBER 2016 clinicianreviews.com Nabiximols, an oral buccal spray, is a com- bination of THC and CBD. It was approved in Canada in 2005 for pain management in can- cer patients and for multiple sclerosis–related pain and spasticity. It is not currently available in the US.2,4 Marijuana use is currently legal in 25 states and the District of Columbia.7,8 However, state laws regarding the criteria for medical use are vague and varied. For example, not all states require that clinicians review risks and ben- efits of marijuana use with patients. Even for those that do, the lack of clinical trials on the safety and efficacy of marijuana make it dif- ficult for clinicians to properly educate them- selves and their patients.9 LIMITATIONS OF RESEARCH Credit: iStock.com/thegoodphoto Why the lack of data? In 1937, a federal tax restricted Despite these obstacles, there is some available marijuana prescription in the US, and in 1942, mari- evidence on medical use of marijuana. A review of juana was removed from the US Pharmacopeia.2,4 the associated risks and potential uses for the sub- The Controlled Substances Act in 1970 designated stance follows. marijuana as a Schedule I drug, a categorization for drugs with high potential for abuse and no currently RISKS ASSOCIATED WITH MARIJUANA USE accepted medical use.9 Following this designation, Acute effects research on marijuana was nearly halted in the US. Most symptoms of marijuana intoxication are at- Several medical organizations have subsequently tributed to the THC component and occur due to called for reclassification to Schedule II in order to the presence of cannabinoid receptors in the central facilitate scientific research into marijuana’s medici- nervous system (see Table 1).5,10 Additional objective nal benefits and risks. signs of acute or chronic intoxication include con- Research is also limited due to the comorbid use junctival injection, tachycardia, cannabis odor, yel- of tobacco and other drugs in study subjects, the lowing of fingertips (from smoking), cough, and food variation of cannabinoid levels among products, cravings.10 and differences in the route of administration—par- A more recently identified effect of long-term ticularly smoking versus oral or buccal routes.5 Con- marijuana use is a paradoxical hyperemesis syn- ducting marijuana research in a fashion similar to drome, in which individuals experience nausea, pharmaceuticals would not only serve the medical vomiting, and abdominal pain. They obtain relief community but also the legislative faction. with hot showers or baths.6,8 Since there is a near absence of cannabinoid re- ceptors in the brain stem, marijuana does not stim- TABLE 1 ulate the autonomic nervous system. It is therefore Effects of Acute Marijuana Intoxication believed that marijuana use cannot be fatal. Cor- roborating this theory, no deaths have been reported Anxiety Increased sociability from marijuana overdose.2,11 Dizziness Laughter Dry mouth Perceptual alterations Withdrawal symptoms Euphoria Relaxation Approximately 10% of regular marijuana users be- Impaired motor function Talkativeness come physically and psychologically dependent on Increased appetite the substance. Once tolerance develops, withdrawal Sources: Hall and Degenhardt. Lancet. 20095; American symptoms occur with cessation of use (see Table 2, Psychiatric Association.10 page 42).2,5,10 Symptoms peak within the first week clinicianreviews.com OCTOBER 2016 • Clinician Reviews 41 MEDICALMARIJUANA TABLE 2 effects of long-term marijuana smoking are incon- Symptoms of Marijuana Withdrawal clusive; some studies have shown potential protec- tive effects.4-6 Other evidence suggests that the risk is Abdominal pain Diaphoresis lower in comparison to tobacco smoking.6 Anger or aggression Fever Cardiovascular. The effects of marijuana on Anorexia or weight loss Headache the cardiovascular system are not fully understood. Anxiety Insomnia Known symptoms include tachycardia, peripheral Chills Irritability vasodilation, hypotension, and syncope.4 There is Craving Restlessness some evidence that marijuana use carries an in- Depression Tremors creased risk for angina in patients with previously established heart disease.5 Patients, especially those Sources: Bostwick. Mayo Clin Proc. 20123; Hall and Degenhardt. Lancet. 20095; American Psychiatric Association.10 with known cardiovascular disease, should be edu- cated about these risks. Reproductive. There are several identified repro- following cessation and may last up to two weeks. Sleep ductive consequences of marijuana use. Research disturbances may occur for more than one month.10 has found decreased sperm count and gynecomastia Unlike with other substances of abuse, there are in men and impaired ovulation in women.4 Studies no pharmaceutical agents to treat marijuana with- on marijuana use in pregnancy consistently reveal drawal; rather, treatment is supportive. Marijuana low birth weight—this effect is, however, less than users often resume use following a period of cessa- that seen with tobacco smoking.5 Other complica- tion in order to avoid withdrawal. tions or developmental abnormalities may occur, but there is currently a lack of evidence to support Chronic effects further conclusions. Dental/oral. Smoking marijuana is associated with Neurologic. The use of marijuana results in short- an increased risk for dental caries, periodontal dis- term memory loss and other cognitive impairments. ease, and oral infections.1 Premalignant oral lesions, There is conflicting evidence as to whether long- such as leukoplakia and erythroplakia, have also term effects remain after cessation.5,6 Because acute been reported. Patient education on the risks and intoxication impairs motor skills, it is associated with need for proper oral hygiene is vital, as are regular increased rates of motor vehicle accidents.6 Driving dental examinations. while under the influence of marijuana should be Respiratory. There are several known pulmonary cautioned against. implications of smoking marijuana, and therefore, Psychiatric. Marijuana use is associated with the this route of administration is not recommended onset and exacerbation of acute psychosis. However, for medicinal use. Respiratory effects of marijuana its role