Medical Marijuana
Prior to the passage of Michigan's Proposal 1 to legalize medical marijuana, I told those who asked me what I thought that I was against it. But, unfortunately it passed and now I'm going to have to deal with it.
Today, I received an e-mail from our hospital's chief medical officer (CMO) to address the issue, since patients are already asking for it; although, the state has several months yet before the program must be implemented in order to develop and set up the program. The CMO also attached a document on FAQ for Proposal 1. It's not clear to me where this document originated, with the hospital or the state, but it unhelpfully states that the Michigan Department of Community Health cannot provide any advice on how patients should grow marijuana plants (for those without a green thumb) nor how patients can legally obtain marijuana. Apparently, patients are only legally allowed to have it once they own it, but there is no one who is legally allowed to supply it to them. Yes, this was well thought out. *rolls eyes*
But that's not why I was against legalizing medical marijuana from the start. I'm not convinced of the benefit of medical marijuana as opposed to drugs that I'm already used to prescribing and I fear the only people who ask for it will be generally drug seeking, leading to a more contentious relationship with some patients. (Even cancer patients sometimes use their medications inappropriately and for recreational purposes.) An editorial by Voth from 2001 notes that "physicians should remember that marijuana remains a schedule I drug, that it has not been approved as safe and efficacious by the Food and Drug Administration, and that the use of marijuana by patients holds inherent risk."
This reminds me of a funny story that I once heard an older oncology researcher tell about an attempted clinical trial of medical marijuana back in the 70s or 80s - because it's not like they've never tried to figure out whether medical marijuana is useful. According to his story, one of the big tobacco companies was actually all set up to start mass producing joints for medical purposes and collaborated with the NIH on a trial meant to prove marijuana was a useful treatment for patients getting chemotherapy. The problem is that these sort of general symptoms, anorexia and nausea, have a psychological compenent as well and can respond to placebo (~20% of the time). So, in order to determine if a medication is really effective, there needs to be a placebo-controlled trial, meaning that one group of patients gets the active medication and another group gets a compound without the active medication. The best trials are double-blinded, meaning that neither the doctor nor the patient knows what the patient is getting to avoid any bias. So, for this attempted trial, patients getting chemotherapy were given either a marijuana joint or a similar thing to smoke that had no marijuana in it. Already this seems like a bad idea because some people are inhaling smoke, which isn't healthy, and have no chance of having any benefit (other than placebo effect, which doesn't count). The funny part of the story, though, came in the description of how, despite the blinding, everyone could tell which patients were getting the actual marijuana and which were getting the placebo...and I understand that this trial was never completed. So, not only has marijuana never been tested to see if it's any better than the very effective modern medications we use for nausea, it's never been tested to see if it's any better than placebo.
The otherwise very helpful medical website for doctors, UpToDate, which contains frequently updated articles on practically every medical issue, written & edited by leaders in each specialty, only says this about the possible therapeutic benefits of medical marijuana (under the general heading of marijuana use in adults):
A systematic review of randomized, controlled trials that evaluated the use of cannabinoids for treatment of chronic pain (including cancer pain, chronic non-malignant pain, and acute postoperative pain) found that cannabinoids were no more effective than codeine in controlling pain, and they have depressant effects that limit their use [102].
The primary active ingredient in marijuana, THC, is available in purified form without other cannabinoids or carcinogens as an oral tablet under the name dronabinol. Other delivery forms currently in development are a transdermal patch, a nasal spray, and a metered dose inhaler. The debate over medicinal use of smoked marijuana will continue.
[102] TI Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.
AU Campbell FA; Tramer MR; Carroll D; Reynolds DJ; Moore RA; McQuay HJ
SO BMJ 2001 Jul 7;323(7303):13-6.
OBJECTIVE: To establish whether cannabis is an effective and safe treatment option in the management of pain. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. STUDY SELECTION: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. DATA EXTRACTION: Independent data extraction; discrepancies resolved by consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.
AD Pain Management Centre, Undercroft, South Block, Queen's Medical Centre, Nottingham NG7 2UH. [removed first author's e-mail address]
PMID 11440935
That article was written by Michael F Weaver, MD (Associate Professor of Internal Medicine and Psychiatry; Medical College of Virginia, Virginia Commonwealth University).
Under the section about anti-nausea medications, it says this about marijuana:
The potential antiemetic utility of cannabinoids was first observed in scattered reports of improved emetic control in patients using marijuana during chemotherapy [31]. Subsequent clinical trials using nabilone and dronabinol (Marinol, a purified synthetic delta-9-tetrahydrocannabinol) confirmed antiemetic activity that was superior to placebo and, in some studies, superior to prochlorperazine [32,33]. In contrast, dronabinol was inferior to metoclopramide in a trial with highly emetogenic chemotherapy [34]. Rigorous comparisons of marijuana with the most effective antiemetic therapies are lacking.
The modest antiemetic activity of this class of agents combined with their relatively unfavorable side effect profile (vertigo, xerostomia, hypotension, dysphoria), especially in older patients, has limited their clinical utility.
[31] TI Medicinal cannabis in oncology practice: still a bridge too far?
AU de Jong FA; Engels FK; Mathijssen RH; van Zuylen L; Verweij J; Peters RP; Sparreboom A
SO J Clin Oncol 2005 May 1;23(13):2886-91.
No abstract provided.
AD Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam--Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
PMID 15860846
[32] TI Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy.
AU Sallan SE; Zinberg NE; Frei E 3rd
SO N Engl J Med 1975 Oct 16;293(16):795-7.
Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents. Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, "double-blind" experiment. All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable. For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001). No patient vomited while experiencing a subjective "high". Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.
PMID 1099449
[33] TI Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine.
AU Sallan SE; Cronin C; Zelen M; Zinberg NE
SO N Engl J Med 1980 Jan 17;302(3):135-8.
Delta-9-tetrahydrocannabinol (THC) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer. In this study we compared THC with prochlorperazine (compazine) in a randomized, double-blind, crossover trial with patients who had failed to benefit from standard antiemetic therapy. Regardless of the emetic activity of the chemotherapeutic agents, there were more complete responses to THC courses (in 36 of 79 courses) than to prochlorperazine (in 16 of 78 courses). Of 25 patients who were treated with both drugs and who expressed a preference, 20 preferred THC (P = 0.005). Among patients under 20 years of age there was a higher proportion of complete responses to THC courses (15 of 20) than among older patients (21 of 59 courses; P = 0.004). Increased food intake occurred more frequently with THC (P = 0.008) and was associated with the presence of a "high." Of 36 THC courses resulting in complete antiemetic responses, 32 were associated with a high. We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective. (N Engl J Med 302:135--138, 1980).
PMID 6985702
[34] Gralla, RJ, Tyson, LB, Bordin, LA, et al. Antiemetic therapy: A review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9- tetrahydrocannabinol. Cancer Treat Rep 1984; 68:163.
no abstract available
That article was written by George F Longstreth, MD (Clinical Professor of Medicine, University of California San Diego School of Medicine) and Paul J Hesketh, MD (Editor - Supportive Care; Professor of Medicine, Tufts University School of Medicine).
My other problem with medical marijuana is that, not only is it not proven to be more efficacious than what I already prescribe, but there are no guidelines for its use. If I do prescribe it, I have no idea what to tell a patient about when or how often they should use it. When I tried to look for any prescribing information, I only found this paper by Nierengarten (Lancet Oncology, November 2007). Unfortunately, I can only see the very beginning of it because I don't have a subscription to Lancet Oncology, but it begins this way: "No evidence-based guidelines are available on dosage or optimum delivery of marijuana for the symptomatic relief of patients with cancer." In the age of evidenced-based medicine, this is a big problem.
Today, I received an e-mail from our hospital's chief medical officer (CMO) to address the issue, since patients are already asking for it; although, the state has several months yet before the program must be implemented in order to develop and set up the program. The CMO also attached a document on FAQ for Proposal 1. It's not clear to me where this document originated, with the hospital or the state, but it unhelpfully states that the Michigan Department of Community Health cannot provide any advice on how patients should grow marijuana plants (for those without a green thumb) nor how patients can legally obtain marijuana. Apparently, patients are only legally allowed to have it once they own it, but there is no one who is legally allowed to supply it to them. Yes, this was well thought out. *rolls eyes*
But that's not why I was against legalizing medical marijuana from the start. I'm not convinced of the benefit of medical marijuana as opposed to drugs that I'm already used to prescribing and I fear the only people who ask for it will be generally drug seeking, leading to a more contentious relationship with some patients. (Even cancer patients sometimes use their medications inappropriately and for recreational purposes.) An editorial by Voth from 2001 notes that "physicians should remember that marijuana remains a schedule I drug, that it has not been approved as safe and efficacious by the Food and Drug Administration, and that the use of marijuana by patients holds inherent risk."
This reminds me of a funny story that I once heard an older oncology researcher tell about an attempted clinical trial of medical marijuana back in the 70s or 80s - because it's not like they've never tried to figure out whether medical marijuana is useful. According to his story, one of the big tobacco companies was actually all set up to start mass producing joints for medical purposes and collaborated with the NIH on a trial meant to prove marijuana was a useful treatment for patients getting chemotherapy. The problem is that these sort of general symptoms, anorexia and nausea, have a psychological compenent as well and can respond to placebo (~20% of the time). So, in order to determine if a medication is really effective, there needs to be a placebo-controlled trial, meaning that one group of patients gets the active medication and another group gets a compound without the active medication. The best trials are double-blinded, meaning that neither the doctor nor the patient knows what the patient is getting to avoid any bias. So, for this attempted trial, patients getting chemotherapy were given either a marijuana joint or a similar thing to smoke that had no marijuana in it. Already this seems like a bad idea because some people are inhaling smoke, which isn't healthy, and have no chance of having any benefit (other than placebo effect, which doesn't count). The funny part of the story, though, came in the description of how, despite the blinding, everyone could tell which patients were getting the actual marijuana and which were getting the placebo...and I understand that this trial was never completed. So, not only has marijuana never been tested to see if it's any better than the very effective modern medications we use for nausea, it's never been tested to see if it's any better than placebo.
The otherwise very helpful medical website for doctors, UpToDate, which contains frequently updated articles on practically every medical issue, written & edited by leaders in each specialty, only says this about the possible therapeutic benefits of medical marijuana (under the general heading of marijuana use in adults):
A systematic review of randomized, controlled trials that evaluated the use of cannabinoids for treatment of chronic pain (including cancer pain, chronic non-malignant pain, and acute postoperative pain) found that cannabinoids were no more effective than codeine in controlling pain, and they have depressant effects that limit their use [102].
The primary active ingredient in marijuana, THC, is available in purified form without other cannabinoids or carcinogens as an oral tablet under the name dronabinol. Other delivery forms currently in development are a transdermal patch, a nasal spray, and a metered dose inhaler. The debate over medicinal use of smoked marijuana will continue.
[102] TI Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.
AU Campbell FA; Tramer MR; Carroll D; Reynolds DJ; Moore RA; McQuay HJ
SO BMJ 2001 Jul 7;323(7303):13-6.
OBJECTIVE: To establish whether cannabis is an effective and safe treatment option in the management of pain. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. STUDY SELECTION: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. DATA EXTRACTION: Independent data extraction; discrepancies resolved by consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.
AD Pain Management Centre, Undercroft, South Block, Queen's Medical Centre, Nottingham NG7 2UH. [removed first author's e-mail address]
PMID 11440935
That article was written by Michael F Weaver, MD (Associate Professor of Internal Medicine and Psychiatry; Medical College of Virginia, Virginia Commonwealth University).
Under the section about anti-nausea medications, it says this about marijuana:
The potential antiemetic utility of cannabinoids was first observed in scattered reports of improved emetic control in patients using marijuana during chemotherapy [31]. Subsequent clinical trials using nabilone and dronabinol (Marinol, a purified synthetic delta-9-tetrahydrocannabinol) confirmed antiemetic activity that was superior to placebo and, in some studies, superior to prochlorperazine [32,33]. In contrast, dronabinol was inferior to metoclopramide in a trial with highly emetogenic chemotherapy [34]. Rigorous comparisons of marijuana with the most effective antiemetic therapies are lacking.
The modest antiemetic activity of this class of agents combined with their relatively unfavorable side effect profile (vertigo, xerostomia, hypotension, dysphoria), especially in older patients, has limited their clinical utility.
[31] TI Medicinal cannabis in oncology practice: still a bridge too far?
AU de Jong FA; Engels FK; Mathijssen RH; van Zuylen L; Verweij J; Peters RP; Sparreboom A
SO J Clin Oncol 2005 May 1;23(13):2886-91.
No abstract provided.
AD Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam--Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
PMID 15860846
[32] TI Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy.
AU Sallan SE; Zinberg NE; Frei E 3rd
SO N Engl J Med 1975 Oct 16;293(16):795-7.
Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents. Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, "double-blind" experiment. All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable. For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001). No patient vomited while experiencing a subjective "high". Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.
PMID 1099449
[33] TI Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine.
AU Sallan SE; Cronin C; Zelen M; Zinberg NE
SO N Engl J Med 1980 Jan 17;302(3):135-8.
Delta-9-tetrahydrocannabinol (THC) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer. In this study we compared THC with prochlorperazine (compazine) in a randomized, double-blind, crossover trial with patients who had failed to benefit from standard antiemetic therapy. Regardless of the emetic activity of the chemotherapeutic agents, there were more complete responses to THC courses (in 36 of 79 courses) than to prochlorperazine (in 16 of 78 courses). Of 25 patients who were treated with both drugs and who expressed a preference, 20 preferred THC (P = 0.005). Among patients under 20 years of age there was a higher proportion of complete responses to THC courses (15 of 20) than among older patients (21 of 59 courses; P = 0.004). Increased food intake occurred more frequently with THC (P = 0.008) and was associated with the presence of a "high." Of 36 THC courses resulting in complete antiemetic responses, 32 were associated with a high. We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective. (N Engl J Med 302:135--138, 1980).
PMID 6985702
[34] Gralla, RJ, Tyson, LB, Bordin, LA, et al. Antiemetic therapy: A review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9- tetrahydrocannabinol. Cancer Treat Rep 1984; 68:163.
no abstract available
That article was written by George F Longstreth, MD (Clinical Professor of Medicine, University of California San Diego School of Medicine) and Paul J Hesketh, MD (Editor - Supportive Care; Professor of Medicine, Tufts University School of Medicine).
My other problem with medical marijuana is that, not only is it not proven to be more efficacious than what I already prescribe, but there are no guidelines for its use. If I do prescribe it, I have no idea what to tell a patient about when or how often they should use it. When I tried to look for any prescribing information, I only found this paper by Nierengarten (Lancet Oncology, November 2007). Unfortunately, I can only see the very beginning of it because I don't have a subscription to Lancet Oncology, but it begins this way: "No evidence-based guidelines are available on dosage or optimum delivery of marijuana for the symptomatic relief of patients with cancer." In the age of evidenced-based medicine, this is a big problem.