National Council on Alcoholism and Drug Dependence - Orange County

Marijuana – Medicine by Legislation

weed-pills It is difficult to open any news medium, whether the local Denver free newspaper or CNN, without encountering an analysis of marijuana policy.  Similar to the division of Americans into politically outspoken reds and blues, passionate factions that either support or oppose wider access to marijuana can be found throughout the nation.  In many states, marijuana policies are now changed because supporters’ influence led to legislative action.  Even though marijuana remains an illegal drug by federal law, several states have passed their own laws saying marijuana is legal for medical treatment and/or recreation.  Legalization of marijuana was discussed in this space last year.  This Update will focus on “medical marijuana.”

“Marijuana” designates a group of herbal or plant products—not a single chemical substance—that derive from strains of Cannabis sativa and Cannabis indica.  The specific chemicals in different samples of marijuana and their relative proportions vary with the origin of the samples.  In general, marijuana contains more than 450 different chemical substances, including 60 or more cannabinoids, the family of chemicals thought responsible for marijuana’s pharmacologic and psychopharmacologic actions.  Delta-9-tetrahydrocannabinol (THC) is the main mood-changing cannabinoid.  Cannabidiol (CBD), which some consider nonpsychoactive, may mediate a number of pharmacologic (possibly therapeutic) effects.

Marijuana as medication is controversial.  Studies of its therapeutic value are limited, and interpretation of the evidence often varies according to the point of view of the interpreter.  Specific cannabinoids that may be consumed orally, however, have been approved as medications in the U.S.  For example, dronabinol, a synthetic THC, is available as Marinol.

How does anything become a medicine?  Under ordinary circumstances, chemical substances that show promise for helping sick people are subjected to a series of rigorous tests before being released.  In this country, the U.S. Food and Drug Administration (FDA) oversees the process.  A candidate substance must pass three phases of investigation before receiving FDA approval, and post-market surveillance of its intended and unintended consequences continues after it is approved for use by prescribers and patients.

Marijuana has not been vetted by this medical-scientific evaluation process.  In fact, the FDA officially states that it “has not approved marijuana as a safe and effective drug for any indication.”  Nevertheless, several states, based on their own political processes, have declared marijuana to be a medicine.

Because marijuana lacks the credentials carried by other medications, including background testing of safety, purity, and efficacy, no physician can prescribe marijuana and no pharmacy can dispense marijuana.  States that declare marijuana to be medicine have to invent other ways to get the substance to the public.  These states generally require a physician to say in writing that an individual has a condition likely to benefit from marijuana.  Then the state issues an identification card stating that the person may possess (and obtain or grow) a modest quantity of marijuana for treatment of their condition.  States often allow “caregivers” to grow marijuana for, and dispensaries to sell marijuana to, individuals with proper medical marijuana cards.

Despite marijuana’s lack of FDA approval and its other-than-ordinary route to medicine status, can marijuana help sick people?  Do the medical benefits of marijuana make all this effort worthwhile?  Or, is the effort shortsighted?  Perhaps the medical benefits of marijuana are overestimated.  Perhaps greater availability of marijuana for medical use will make more marijuana available for misuse, especially by vulnerable young people.  If you ask these questions, the answers you receive will depend very much upon whom you ask.

Is there evidence that marijuana can be medicine?  On one hand, many individuals have stated publically that marijuana has been the only substance that relieved their condition.  On the other hand, scientific evidence of marijuana’s efficacy as a medicine is limited and the results are variable.  This shortage of scientific information is in part because researchers have focused more on potential harm from marijuana than on potential benefits.  For example, of approximately 2,000 recent peer-reviewed articles on the effects of marijuana in the U.S. National Library of Medicine, only about 6 percent investigated potential benefits.

Randomized controlled trials (RCTs) are the gold standard for evaluating the effectiveness of medications, yet RCTs represent only a small proportion of the published research on marijuana.  We summarize some of the available research here.  For more detail, we’ve provided References and links.  Be advised, however, that some links offer the full text of a journal article while others offer only an abstract or opportunity to purchase the article.  (To explore scientific literature without incurring a lot of expense, consider working with a library, especially an academic library.)

Marijuana may have potential as an anti-inflammatory agent and may ease symptoms of the inflammatory disease multiple sclerosis (MS), such as muscle stiffness and spasm, certain types of pain, and overactive bladder.  A combination of THC and CBD administered as an oral spray (Sativex) is used to treat MS in other countries and is in phase 3 clinical trials in the U.S.  Smoked marijuana may have potential for treating chronic pain; some think medical marijuana will decrease problems related to opioid pain medicines; others worry that any potential benefit will be outweighed by the risk of rewarding effects (addiction).  In one study, smoked marijuana was associated with mild relief from standardized pain, but only at a modest dose.  A higher dose was associated with increased perception of pain.

In glaucoma, marijuana appears to lower pressure inside the eye; but marijuana may also lower blood pressure to the point of causing symptoms.  Some experts consider conventional treatments for glaucoma superior to marijuana.  Marijuana/dronabinol has decreased vomiting in patients receiving cancer chemotherapy, but long-term use has also been associated with increased vomiting.  Again, some experts consider conventional treatments for vomiting superior to marijuana.  Marijuana may increase appetite in wasting syndromes such as AIDS, but the benefit may come at the cost of cognitive impairment. 

It is incumbent on all professionals to take into account the potential risks of their treatments as well as the potential benefits.  There is definitive evidence that marijuana can cause some types of harm and suggestive evidence it can cause others.  Addiction is one clear risk; with that risk likely magnified in recent years because the concentration of THC in available specimens rose from 3 to 12 percent between the 1980s and 2012.

Approximately 9 percent of people exposed to marijuana become addicted.  If individuals start smoking in their teenage years, however, this increases to 17 percent.  If they smoke daily, their risk of addiction is 25 to 50 percent.  An estimated 2.7 million people in the U.S. meet criteria for cannabis dependence.  The sheer size of this population heightens concern about some problems associated with marijuana use, such as lower grades in school and greater of risk of dropping out.  Furthermore, heavy marijuana use is associated with lower income, unemployment, lower satisfaction with life, and criminal behavior.

Young brains exposed to marijuana may not develop normally.  Marijuana may contribute to the development of schizophrenia in those who are genetically vulnerable.  Marijuana use may also lead to symptoms of depression and anxiety even though some people smoke marijuana to relieve those same symptoms.

People who use marijuana to relieve one medical condition may develop another medical condition.  For example, regular marijuana smoking injures the lining of large airways in the lungs and contributes to chronic bronchitis.  Light and moderate marijuana smoking may not lead to chronic obstructive pulmonary disease or lung cancer; but heavy marijuana smoking may do both.

People who support wider access to marijuana often view it as less harmful than alcohol.  Regardless of their pecking order, both can be hazardous.  The risk of a motor vehicle crash is 5 times higher than usual for a person with a blood alcohol level above 0.08 percent.  It’s 27 times higher for persons under the age of 25.  Crash risk is estimated to be 3 to 7 times higher for those with a detectable level of tetrahydrocannabinol (1 ng/mL THC).  Using both substances at the same time may be worse because alcohol can compromise drivers’ ability to consciously compensate for impairment due to marijuana.  Marijuana opponents predicted that the legalization of pot—on top of medical marijuana—in Colorado and Washington would lead to more traffic crashes and related deaths.  While claims have been made in both directions, some analysts say there is not yet enough data to know.

Consumers of conventional medicines, whether prescribed or over-the-counter, by and large know what they are taking and how to take it.  Labels specify the recommended dose (usually in milligrams) and convey instructions from the prescriber and/or manufacturer.  Not so for medical marijuana.  Marijuana products are not standardized; the ingredients of a Cannabis strain or marijuana cookie or candy are not confirmed and may not be consistent.  This makes targeting symptom relief in a consistent manner difficult and potentially dangerous.  Excessive marijuana can produce extreme anxiety or even psychosis, which can put the individual and others in danger.

States that have adopted marijuana as medicine have begun their own clinical trials of this substance without the medical, scientific, and ethical oversight that usually protects us from shortsighted clinical enthusiasm and conflicts of interest.  One potential conflict:  believers in the advantages of “medical marijuana” may be influenced by their belief in the advantages of the legalization of marijuana, and their adherence to the misconception that marijuana is a harmless substance.

Facts are limited.  Many analyses of marijuana policy are biased.  Marijuana may have potential for medical benefit.  At the same time we have clear medical-scientific evidence of marijuana’s potential for harm.  Clinical trials of marijuana as medicine have begun.  The largest trials are neither randomized nor controlled.  Rigorous scientific study, particularly epidemiologic investigations of these statewide therapeutic trials, will provide better information to make decisions that are fair to marijuana’s potential and to the health of the public.

To think about:  ”The greatest derangement of the mind is to believe in something because one wishes it to be so.”   -- Louis Pasteur

The NCADD Addiction Medicine Update provides NCADD Affiliates and the public with authoritative information and commentary on specific medical and scientific topics pertaining to addiction and recovery.

References

[1] Koppel BS, Brust JCM, Fife T, et al.  Systematic review:  Efficacy and safety of medical marijuana in selected neurologic disorders:  Report of the Guideline Development Subcommittee of the American Academy of Neurology.  Neurology 2014;82;1556-1563     a. http://www.neurology.org/content/82/17/1556.full.pdf+html

[2] Collin C, Davies P, Mutiboko IK, Ratcliffe S.  Randomized  controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.  Eur J 2007; 14:290-6. http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2006.01639.x/full

[3]Centonze D, Mori F, Koch G, et al.   Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis.  Neurol Sci 2009; 30:531-4 http://link.springer.com/article/10.1007/s10072-009-0136-5#

[4] Nagarkatti P, Pander R, Raeder SA, Hedge VL, Nagarkatti M.  Cannabinoids as novel anti-inflammatory drugs.  Future Med Chem 2009;1:1333-49. http://www.future-science.com/doi/abs/10.4155/fmc.09.93

[5] Esposito G, Fillippis DD, Carlo C, et al.  Cannabidiol in inflammatory bowel diseases: a brief overview.  Phytoher Res 2013;5:633-6 http://onlinelibrary.wiley.com/doi/10.1002/ptr.4781/full

[6] Wolsey B, Marquette T, Tsodikov A, et al.  A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 2008;9:506-21 http://www.sciencedirect.com/science/article/pii/S1526590008003696

[7] Wallace M, Schulteis G, Atkinson JH, et al.  Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers.  Anesthesiology 2007;107”785-96.http://journals.lww.com/anesthesiology/Fulltext/2007/11000 Dose_dependent_Effects_of_Smoked_Cannabis_on.16.aspxEndocannabinoid

[8] Cooper ZD, Comer SD, Haney M.  Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers.  Neuropsychopharmacology 2013;38:1984-92 http://www.nature.com/npp/journal/v38/n10/abs/npp201397a.html

[9] Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbard SS.  Effects of marijuana on intraocular and blood pressure in glaucoma.  Ophthalmology 1980;87:222-8. http://www.sciencedirect.com/science/article/pii/S0161642080352585

[10] Hepler RS, Frank IR.  Marijuana smoking and intraocular pressure. JAMA 1971;217:1392 http://jama.jamanetwork.com/article.aspx?articleid=338934

[11] Nucci C, Bari M, Spano A, et al. Potential roles of (endo) cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection. Prog Brain Res 2008;173:451-64.http://www.sciencedirect.com/science/article/pii/S007961230801131X

[12] Sallan SE, Zinberg NE, Frei E III. Antiemetic effects of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Eng J Med 1975;293:795-7. http://www.nejm.org/doi/pdf/10.1056/NEJM197510162931603

[13] D’Souza G, Matson PA, Grady CD, et al. Medicinal and recreational marijuana use among HIV-infected women in the Women’s Interagency HIV Study (WIHS) cohort, 1994-2010. J Acquire Immune Deific  Syndr 2012;61:618-26.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508315/

[14] Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet 2009;374:1383-91.http://www.sciencedirect.com/science/article/pii/S0140673609610370

[15] Center for Behavioral Health Statistics and Quality. National survey on drug use and health. Rockville, MD; Substance Abuse & Mental Health Services Administration, 2013

[16] Bray JW, Zarkin GA, Ring Walt C, Qi J. The relationship between marijuana initiation and dropping out of high school. Health Econ 2000;9:9-18. http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1050(200001)9:1%3C9::AID-HEC471%3E3.0.CO;2-Z/full

[17] Lyn key M, Hall W. The effects of adolescent cannabis use on educational attainment: a review.  Addiction 2000;95:1621-30. http://onlinelibrary.wiley.com/doi/10.1046/j.1360-0443.2000.951116213.x/abstract

[18] Fergusson DM, Boden JM. Cannabis use and later life outcomes. Addiction 2008;103:969-76.http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2008.02221.x/full

[19] Brook JS, Lee JY, Finch SJ, Seltzer N, Brook DW. Adult work commitment, financial stability, and social environment as related to trajectories of marijuana use beginning in adolescence. Subset Abus 2013;34:298-305. http://www.tandfonline.com/doi/abs/10.1080/08897077.2013.775092

[20] Tashkin DP. Effects of marijuana smoking on the lung. Ann Am Thorax Soc 2013;10:239-47. http://www.atsjournals.org/doi/abs/10.1513/annalsats.201212-127fr

[21] Hash be M, Morgenstern H, Cui Y, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-base case-control study. Cancer Epidemiology Biomarkers Prey 2006;15:1829-34.

[22] Pistils M, Perra S, Pillolla G, Melis M, Muntoni AL, Gesso GL. Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry 2004;56:86-94.http://www.sciencedirect.com/science/article/pii/S000632230400530X

[23] DiNieri JA, Wang X, Szutorisz H, et al. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry 2011;70:763-9.n http://www.sciencedirect.com/science/article/pii/S000632231100672X

[24] Caspi A, Moffitt TE, Cannon M, et al.  Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environmental interaction. Biol Psychiatry 2005;57:1117-27. http://www.sciencedirect.com/science/article/pii/S0006322305001034

[25] Patton GC, Coffey C, Carlin JB, Degenhardt L, Lyn key M, Hall W. Cannabis use and mental health in young people: cohort study. BMJ 2002;325:1195-8. http://www.bmj.com/content/325/7374/1195.1?variant=full-text&rss=1&ssource=mfr

[26] Peck RC, Gebers MA, Vows RB, Romano E.  The relationship between blood alcohol concentration (BAC), age, and crash risk. J Safety Res 2008; 39:311-9. http://www.sciencedirect.com/science/article/pii/S0022437508000509

[27] Remailer JG, Berthas G, van Laar M, Drummer OH. Dose related risk of motor vehicle crashes after cannabis use. Drug Alcohol Depend 2004;73:109-19. http://www.sciencedirect.com/science/article/pii/S0376871603002849

[28] Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem 2013;59:478-92. http://www.clinchem.org/content/59/3/478.short

[29] Stacy Salomonsen-Sautel, Sung-Joon Min, Joseph T. Sakai, Christian Thurston, Christian Hoofer. Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado. Drug and Alcohol Dependence, 2014; DOI: 10.1016/j.drugalcdep.2014.04.008. and  http://www.sciencedirect.com/science/article/pii/S0376871614008345

[30} http://www.cnn.com/2014/07/12/health/marijuana-researcher-arizona/index.html...