[IMGL="white"]http://www.drugs-forum.com/forum/attachment.php?attachmentid=33361&stc=1&d=1370716248[/IMGL]Twenty states and Washington DC have now legalized the use of medical cannabis.
With all the attention legalized medical marijuana has been receiving, it is curious that very little attention was given to this topic during the recent APA meeting in San Francisco. It was particularly ironic because on May 18 and 19, San Francisco hosted the International Cannabis and Hemp Expo, which promoted the culture of cannabis use. All you needed to gain entry was $15 and a medical complaint. . . such as insomnia or back pain.
Given the omission of meaningful discussion during the APA meeting—and the apparent confusion on the part of many psychiatrists about prescribing the substance and the ethical issues that it poses for many, Psychiatric Times is following up with a survey on the topic. Psychiatrists are invited to complete the survey and give their candid feedback on the subject.
Many of our patients have started asking if they are candidates for a prescription. I am a geriatric psychiatrist, and I have seen a surge in the use of marijuana (whether medicinal or not) by aging adults who may have used it in their youth. It is frequently provided to the elderly by their middle-aged children for pain, insomnia, anxiety, weight loss and—more recently—for the agitation associated with dementia. Many report improvement in these symptoms, and ask me to approve the use of medical marijuana throughout the day to help “mellow out” their parent. (The use of medical cannabis is legal in California where I practice.) This request puts me in the awkward situation of having to know about — and unwillingly consent to — marijuana use but not being able to prevent it. As a psychiatrist, I don’t feel that I can ethically approve any drug abuse in older adults.
Cannabis is commonly regarded as an innocuous drug. The prevalence of lifetime and regular use has increased continuously in most developed countries. However, accumulating evidence highlights the risks of dependence and other adverse effects, particularly among people with pre-existing psychiatric disorders. We all know that the use of marijuana in the context of psychiatric illness can worsen symptoms (eg, it can increase anxiety and paranoia). Others report that marijuana diminishes their symptoms of anxiety, sleep, or pain. Long-term use of marijuana can also cause apathy and low motivation. An appreciable proportion of cannabis users report short-lived adverse effects, including psychotic states, following heavy consumption, and regular users are at risk of dependence. People with major mental illnesses such as schizophrenia are especially vulnerable in that cannabis generally provokes relapse and aggravates existing symptoms.
Cannabis is a risk-factor for mental illness. It can cause or create:
At the same time, there is still no evidence for the use of medicinal marijuana for most disorders. Some evidence suggests that it helps in nausea (eg, in patients receiving chemotherapy), muscle spasticity in spinal cord injuries, and in some cases neuropathic pain. Marijuana is still classified as a Schedule I drug (in the same category as LSD, PCP, and methamphetamines), while cocaine, for example, is classified as a Schedule II drug. This limits the ability of researchers to explore potential medical uses for marijuana.
- Psychological responses such as panic, anxiety, depression or psychosis. These effects may be described as “toxic” in that they generally relate to excess consumption of the drug.
- Effects on pre-existing mental illness.
- Dependency or withdrawal effects.
Given the paucity of evidence for the uses of medicinal cannabis, and still very unclear and conflicting local and federal laws, physicians will be careful in prescribing medicinal marijuana.
We are curious to know what your opinions may be with respect to prescribing medicinal cannabis. We will later review and summarize the results of the survey for our readers.
By Helen Lavretsky, MD, MS
[Editor's note: The New England Journal of Medicine recently polled physicians across specialties about their views on medicinal use of marijuana. The case vignette that was presented and the comments -- pros and con -- that it elicited can be viewed /here.]
OR RIGHT HERE:
Medicinal Use of Marijuana — Polling Results
Jonathan N. Adler, M.D., and James A. Colbert, M.D. New England Journal Medicine 2013; 368:e30May 30, 2013
Readers recently joined in a lively debate about the use of medicinal marijuana. In Clinical Decisions, an interactive feature in which experts discuss a controversial topic and readers vote and post comments, we presented the case of Marilyn, a 68-year-old woman with metastatic breast cancer. We asked whether she should be prescribed marijuana to help alleviate her symptoms. To frame this issue, we invited experts to present opposing viewpoints about the medicinal use of marijuana. J. Michael Bostwick, M.D., a professor of psychiatry at Mayo Clinic, proposed the use of marijuana “only when conservative options have failed for fully informed patients treated in ongoing therapeutic relationships.” Gary M. Reisfield, M.D., from the University of Florida, certified in anesthesiology and pain medicine, and Robert L. DuPont, M.D., a clinical professor of psychiatry at Georgetown Medical School, provide a counterpoint, concluding that “there is little scientific basis” for physicians to endorse smoked marijuana as a medical therapy.
We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries. A total of 1446 votes were cast from 72 countries and 56 states and provinces in North America, and 118 comments were posted. However, despite the global participation, the vast majority of votes (1063) came from the United States, Canada, and Mexico. Given that North America represents only a minority of the general online readership of the Journal, this skew in voting suggests that the subject of this particular Clinical Decisions stirs more passion among readers from North America than among those residing elsewhere. Analysis of voting across all regions of North America showed that 76% of voters supported medicinal marijuana. Each state and province with at least 10 participants casting votes had more than 50% support for medicinal marijuana except Utah. In Utah, only 1% of 76 voters supported medicinal marijuana. Pennsylvania represented the opposite extreme, with 96% of 107 votes in support of medicinal marijuana.
Outside North America, we received the greatest participation from countries in Latin America and Europe, and overall results were similar to those of North America, with 78% of voters supporting the use of medicinal marijuana. All countries with 10 or more voters worldwide were at or above 50% in favor. There were only 43 votes from Asia and 7 votes from Africa, suggesting that in those continents, this topic does not resonate as much as other issues.
Where does this strong support for medicinal marijuana come from? Your comments show that individual perspectives were as polarized as the experts' opinions. Physicians in favor of medicinal marijuana often focused on our responsibility as caregivers to alleviate suffering. Many pointed out the known dangers of prescription narcotics, supported patient choice, or described personal experience with patients who benefited from the use of marijuana. Those who opposed the use of medicinal marijuana targeted the lack of evidence, the lack of provenance, inconsistency of dosage, and concern about side effects, including psychosis. Common in this debate was the question of whether marijuana even belongs within the purview of physicians or whether the substance should be legalized and patients allowed to decide for themselves whether to make use of it.
In sum, the majority of clinicians would recommend the use of medicinal marijuana in certain circumstances. Large numbers of voices from all camps called for more research to move the discussion toward a stronger basis of evidence.
Medicinal Use of Marijuana
New England Journal of Medicine 368;9 february 28, 2013
Interactive at nejm.org
This interactive feature addresses the approach to a clinical issue. A case vignette is followed by specific options, neither of which can be considered either correct or incorrect. In short essays, experts in the field then argue for each of the options. In the online version of this feature, available at NEJM.org, readers can participate in forming community opinion by choosing one of the options and, if they like, providing their reasons.
Marilyn is a 68-year-old woman with breast cancer metastatic to the lungs and the thoracic and lumbar spine. She is currently undergoing chemotherapy with doxorubicin. She reports having very low energy, minimal appetite, and substantial pain in her thoracic and lumbar spine. For relief of nausea, she has taken ondansetron and prochlorperazine, with minimal success. She has been taking 1000 mg of acetaminophen every 8 hours for the pain. Sometimes at night she takes 5 mg or 10 mg of oxycodone to help provide pain relief. During a visit with her primary care physician she asks about the possibility of using marijuana to help alleviate the nausea, pain, and fatigue. She lives in a state that allows marijuana for personal medicinal use, and she says her family could grow the plants. As her physician, what advice would you offer with regard to the use of marijuana to alleviate her current symptoms? Do you believe that the overall medicinal benefits of marijuana outweigh the risks and potential harms?
Which one of the following approaches do you find appropriate for this patient? Base your choice on the published literature, your clinical experience, recent guidelines, and other sources of information.
Option 1: Recommend the Medicinal Use of Marijuana
Option 2: Recommend against the Medicinal Use of Marijuana
Recommend the Medicinal Use of Marijuana
J. Michael Bostwick, M.D.
Within established doctor–patient relationships, I endorse thoughtful prescription of medicinal marijuana for patients in situations similar to Marilyn's. A largely anecdotal but growing literature supports its efficacy, particularly for pain or nausea that is unresponsive to mainstream treatments.1 In 1970, marijuana was designated a Schedule I drug under the Controlled Substances Act, a classification indicating a high potential for abuse and a lack of medical value.2 But physicians face a catch-22: although 18 states have legalized medicinal marijuana, physicians in those states who write prescriptions violate the law of the land.
Federal policy has failed to keep pace with recent scientific advances. Laboratory research has elucidated the far-flung endocannabinoid system that modulates neurotransmitter networks throughout the body through cannabinoid-1 (CB1) receptors that are preferentially distributed in the brain and cannabinoid-2 (CB2) receptors that are prominent in gut and immune tissues. Among dozens of cannabinoids in raw marijuana, two show medicinal promise. The first, Δ9-tetrahydrocannabinol (Δ9-THC), is the CB1 ligand that recreational users prize. The second, cannabidiol (CBD), acting on CB2, lacks psychoactivity but works synergistically with Δ9-THC to minimize “highs” and maximize analgesia.2,3
Arguments for and against medicinal marijuana are manifold. Under federal law, the drug is illegal. However, given widespread state defiance, the cannabis horse long ago burst from the federal jurisdictional barn. In Colorado, a handful of physicians write half the state's prescriptions for medicinal marijuana, for questionable indications.4 Just because a few rogue doctors flout lax legislation to abet pot-mill commerce, that doesn't justify depriving all physicians of the right to prescribe medicinal marijuana. No trials under the auspices of the Food and Drug Administration (FDA) have compared medicinal marijuana with traditional analgesics.5
Because of marijuana's Schedule I status, industry is thwarted in its attempts to develop compounds with endocannabinoid agonist or antagonist qualities that might have analgesic, appetite-modulatory, immunosuppressant, antiemetic, neuroleptic, or antineoplastic effects, among other possibilities.2 Some people may contend that dose determination by patients deviates from modern medical practice,3,6 but adjustment of medications by patients is ubiquitous in hospitals through patient-controlled analgesia pumps. Some people argue that as a drug of abuse, marijuana has no business being used for clinical purposes. Yet, several Schedule I drugs have close cousins with legitimate medical applications. Heroin and morphine derivatives have an illicit–licit kinship, as do “ecstasy” (3,4-methylenedioxymethamphetamine) and stimulant drugs central to the treatment of attention deficit–hyperactivity disorder, as well as phencyclidine and ketamine, an anesthetic agent.2
Meanwhile, Marilyn seeks relief from the consequences of metastatic breast cancer. Neither acetaminophen nor oxycodone has proven to be effective against the serious pain of spinal and visceral metastases. Neither ondansetron nor prochlorperazine has relieved the nausea, which may have been induced by doxorubicin. More aggressive narcotics could be prescribed (risking the worsening of gastrointestinal symptoms), but Marilyn asks her doctor whether medicinal marijuana might offer the singular advantage of reducing pain and nausea simultaneously.
Inhaled pharmaceuticals are commonplace, but in the United States no vaporized inhalant is currently available as an alternative to medicinal marijuana, pending FDA approval of nabiximols, currently in phase 3 trials (ClinicalTrials.gov number, 01337089).6 With slow onset and unreliable bioavailability, oral cannabinoids are ill suited to relieving Marilyn's acute distress.2 If she had no recreational experience with marijuana, Marilyn could find medicinal marijuana's psychoactive effects unacceptable, although noxious psychoactivity also limits opiate use. Should Marilyn experience benefit, however, she would channel 5000 years of medical history, including the century when cannabis derivatives routinely resided in American doctors' black bags.1
In sum, I believe that physicians who prescribe medicinal marijuana should do so only when conservative options have failed for fully informed patients treated in ongoing therapeutic relationships. As federal gridlock prevents much-needed research, patients such as Marilyn deserve the potential relief that medicinal marijuana affords.
Recommend against the Medicinal Use of Marijuana
Gary M. Reisfield, M.D., Robert L. DuPont, M.D.
Marilyn's query should be recognized both for the words — a straightforward question about medicinal marijuana use — and for the music — a plea for symptom relief. Both must be addressed. Although marijuana probably involves little risk in this context, it is also unlikely to provide much benefit. Simply to allow a patient with uncontrolled symptoms of metastatic breast cancer to leave the office with a recommendation to smoke marijuana is to succumb to therapeutic nihilism.6
There is burgeoning interest in the therapeutic potential of targeting the endocannabinoid system. Although most of the research into this system involves the use of specific cannabinoids, a small body of high-quality research shows evidence of clinically significant analgesia from smoked marijuana, primarily for neuropathic pain. There is little evidence to support the use of smoked marijuana for Marilyn's nociceptive pain, and less still for her other symptoms.
Smoked marijuana is a nonmedical, nonspecific, and potentially hazardous method of drug delivery. The cannabis plant contains hundreds of pharmacologically active compounds, most of which have not been well characterized. Each dispensed quantity of marijuana is of uncertain provenance and of variable and uncertain potency and may contain unknown contaminants.
There are other questions to consider in Marilyn's case. Could marijuana's cognitive side effects, particularly its effects on memory, promote or exacerbate chemotherapy-induced cognitive dysfunction? If Marilyn's pulmonary disease includes lymphangitic spread, could smoking cause hypoxemia? What effects will marijuana's potential immunologic hazards (e.g., chemical constituents, pyrolized gases, viable fungal spores, or pesticide residues) have on her health during periods of immunocompromise?7 How will marijuana, alone or in combination with other medications associated with potential cognitive and psychomotor impairment, affect her ability to safely operate a motor vehicle?8 What are the possible effects of marijuana on tumor progression? The putative cannabinoid receptor GPR55 (G-protein–coupled receptor 55) is expressed in human breast cancers, with higher levels of expression correlated with more aggressive phenotypes.9 The marijuana constituent Δ9-THC has been shown in some studies to act as a GPR55 agonist, raising the possibility that it can promote cancer-cell proliferation.10
Two prescription cannabinoids are available, dronabinol (Marinol) (a synthetic Δ9-THC) and nabilone (Cesamet) (a Δ9 -THC congener), which are FDA-approved for the treatment of chemotherapy-induced nausea and vomiting. These medications have shown efficacy in the management of pain and distress. In contrast to smoked marijuana, they feature oral administration, chemical purity, precise dosages, and a slower onset but sustained duration of action. They may be less likely than smoked marijuana to induce anxiety, panic, and negative mood states,11 but they have otherwise similar side-effect profiles.
Cannabinoids, however, should be used only as lower-tier therapies for chemotherapy-induced nausea and vomiting, since other medications, such as 5-hydroxytryptamine3-receptor antagonists, dexamethasone, and aprepitant, have superior efficacy and fewer side effects.12
Assure Marilyn — and follow through on the assurance — that throughout her illness she will be accompanied, cared for, and helped to live as well and as long as possible. Reassure her that meticulous attention will be paid to symptom relief. Discuss the patient-specific potential risks and benefits of smoked marijuana and of the administration of pharmaceutical cannabinoids. There is little scientific basis for recommending that she smoke marijuana for symptom control. As Bernard Lown remarked, “Caring without science is well-intentioned kindness, but not medicine.”13
1 Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical marijuana: clearing away the smoke. Open Neurol J 2012;6:18-25.
2 Bostwick JM. Blurred boundaries: the therapeutics and politics of medical marijuana. Mayo Clin Proc 2012;87:172-86.
3 Mechoulam R. Cannabis — a valuable drug that deserves better treatment. Mayo Clin Proc 2012;87:107-9.
4 Nussbaum AM, Boyer JA, Kondrad EC. “But my doctor recommended pot”: medical marijuana and the physician-patient relationship. J Gen Intern Med 2011;26:1364-7.
5 Bowles DW, O’Bryant CL, Camidge DR, Jimeno A. The intersection between cannabis and cancer in the United States. Crit Rev Oncol Hematol 2012;83:1-10.
6 Kleber JD, DuPont RL. Physicians and medical marijuana. Am J Psychiatry 2012;169:564-8.
7 McPartland JM, Pruitt PL. Medical marijuana and its use by the immunocompromised. Altern Ther Health Med 1997;3:39-45.
8 Battistella G, Fornari E, Thomas A, et al. Weed or wheel! FMRI, behavioural, and toxicological investigations of how cannabis smoking affects skills necessary for driving. PLoS One 2013;8(1):e52545.
9 Henstridge CM. Off-target cannabinoid effects mediated by GPR55. Pharmacology 2012;89:179-87.
10 Sharir H, Abood ME. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther 2010;
11 Moreira FA, Grieb M, Lutz B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists:
focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab 2009;23:133-44.
12 Irvin W Jr, Muss HB, Mayer DK. Symptom management in metastatic breast cancer. Oncologist 2011;16:1203-14.
13 Lown B. The lost art of healing: practicing compassion in medicine. Boston: Houghton Mifflin, 1996.
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