Marijuana


Article Author:
Anisha Turner


Article Editor:
Suneil Agrawal


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Mayank Singhal


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Updated:
10/9/2019 1:50:43 PM

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. [1][2][3][4]

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. [5]

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.[6][7][8][9]

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.[10][11]

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.[12][13]

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.[14][15]

Enhancing Healthcare Team Outcomes

There is a vast amount of literature on marijuana and its health benefits. Unfortunately, the majority of these are anecdotal reports. Without clinical trials and lack of a universal formula of marijuana, there appear to be significant controversies in the clinical benefits of marijuana. All healthcare workers including nurse practitioners and pharmacists should educate patients that marijuana may not be the panacea for all medical disorders. Todate, marijuana has been shown to improve appetite and reduce mild nausea. Until data from randomized clinical trials are available, the prescription of marijuana should be limited as more evidence seems to indicate that this product may not be entirely safe for long term consumption.[16][17][18]


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Marijuana - Questions

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What is the active constituent of marijuana?



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Which of the following is a therapeutic indication for dronabinol?



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Which of the following does not cause cardiac toxicity?



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A 13-year-old child is brought in by his mother because he is acting strangely. He has become "lazier" at school and, as a result, his grades have decreased. She believes that he has been more depressed because he spends his free time sitting in his room and eating more than usual. On physical exam, you notice injected conjunctivae but no other pertinent findings. What is the best next step?



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What is one proven therapeutic indication for marijuana?



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Marijuana - References

References

Eichhorn Bilodeau S,Wu BS,Rufyikiri AS,MacPherson S,Lefsrud M, An Update on Plant Photobiology and Implications for Cannabis Production. Frontiers in plant science. 2019;     [PubMed]
Bashqoy F,Heizer JW,Reiter PD,Wang GS,Borgelt LM, Increased Testing and Health Care Costs for Pediatric Cannabis Exposures. Pediatric emergency care. 2019 Apr 12;     [PubMed]
Wilson MM,Masterson E,Broglio K, Cannabis Use among Patients in a Rural Academic Palliative Care Clinic. Journal of palliative medicine. 2019 Apr 17;     [PubMed]
Kisková T,Mungenast F,Suváková M,Jäger W,Thalhammer T, Future Aspects for Cannabinoids in Breast Cancer Therapy. International journal of molecular sciences. 2019 Apr 3;     [PubMed]
Premoli M,Aria F,Bonini SA,Maccarinelli G,Gianoncelli A,Pina SD,Tambaro S,Memo M,Mastinu A, Cannabidiol: Recent advances and new insights for neuropsychiatric disorders treatment. Life sciences. 2019 May 1;     [PubMed]
Posis A,Bellettiere J,Liles S,Alcaraz J,Nguyen B,Berardi V,Klepeis NE,Hughes SC,Wu T,Hovell MF, Indoor cannabis smoke and children's health. Preventive medicine reports. 2019 Jun;     [PubMed]
Freeman TP,Hindocha C,Green SF,Bloomfield MAP, Medicinal use of cannabis based products and cannabinoids. BMJ (Clinical research ed.). 2019 Apr 4;     [PubMed]
Ugradar S,Manta A,Flanagan D, Unilateral cilioretinal artery occlusion following cannabis use. Therapeutic advances in ophthalmology. 2019 Jan-Dec;     [PubMed]
Drummer OH,Gerostamoulos D,Woodford NW, Cannabis as a cause of death: A review. Forensic science international. 2019 Mar 14;     [PubMed]
Chadi N,Levy S, What every pediatric gynecologist should know about marijuana use in adolescents. Journal of pediatric and adolescent gynecology. 2019 Mar 25;     [PubMed]
Giano Z,Hubach RD,Currin JM,Wheeler DL, Adverse childhood experiences and MSM marijuana use. Drug and alcohol dependence. 2019 May 1;     [PubMed]
Cavazos-Rehg PA,Krauss MJ,Cahn E,Lee KE,Ferguson E,Rajbhandari B,Sowles SJ,Floyd GM,Berg C,Bierut LJ, Marijuana Promotion Online: an Investigation of Dispensary Practices. Prevention science : the official journal of the Society for Prevention Research. 2019 Feb;     [PubMed]
Kahan M,Srivastava A, New medical marijuana regulations: the coming storm. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2014 Sep 2;     [PubMed]
Wolfe CE,Wood DM,Dines A,Whatley BP,Yates C,Heyerdahl F,Hovda KE,Giraudon I,Dargan PI, Seizures as a complication of recreational drug use: Analysis of the Euro-DEN Plus data-set. Neurotoxicology. 2019 Apr 8;     [PubMed]
Koltai H,Poulin P,Namdar D, Promoting cannabis products to pharmaceutical drugs. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2019 Apr 30;     [PubMed]
Wisk LE,Levy S,Weitzman ER, Parental views on state cannabis laws and marijuana use for their medically vulnerable children. Drug and alcohol dependence. 2019 Feb 14;     [PubMed]
Artukoglu BB,Bloch MH, The Potential of Cannabinoid-Based Treatments in Tourette Syndrome. CNS drugs. 2019 Apr 11;     [PubMed]
Friedman D,French JA,Maccarrone M, Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders. The Lancet. Neurology. 2019 May;     [PubMed]

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