2009 Medical Marijuana Update

Posted on Friday, January the 16th at 9:21pm

By: Dr. Stephen F. Grinstead, LMFT, ACRPS, CADC-II

I still find that the some of the old controversies about the use of medical marijuana continue since I first published my Medical Marijuana Controversy article in 2002. One of these issues concerns the use of marijuana as a legitimate medication. Since that original article there has been more quality research into the use of some of the components of marijuana as legitimate and effective medication.

In 2008 Medscape.com published an online report titled Opioid and Nonopioid Therapies for the Management of Pain by Lynn R. Webster, MD, FACPM, FASAM based on research presented at the American Academy of Pain Medicine 2007 Conference. One section of this report was the use of cannabinoids as a non-opiate alternative. Dr. Webster stated in that report:

Cannabinoids have demonstrated significant analgesic properties, but problems with side effects remain. Newer compounds show promise for analgesic efficacy while reducing common side effects of dizziness, euphoria, fatigue, and nausea.

An oral mucosal spray (Sativex, GW Pharmaceuticals) that contains 2.7 mg of delta-9-tetrahydrocannabinol (THC) and 2.5 mg of cannabidiol (CBD) has been well tolerated in clinical studies. The co-administration of CBD appears to reduce the psychoactive effects of THC, and intoxication is less than with oral THC, according to presenters at AAPM. Patients are allowed to self-titrate, resulting in an average dose of approximately 20-30 mg/day of both THC and CBD. A double-blind, randomized, placebo-controlled study of 160 outpatients with multiple sclerosis (MS) reported significant reduction of spasticity with the cannabis-based medicinal extract (CBME) (Sativex) compared to placebo (P = .001). A pooled analysis across 3 phase 3 MS spasticity studies, incorporating 666 patients, showed that CBME oral mucosal spray was significantly superior to placebo (P < .05).

The CBME compound has been approved in Canada to treat neuropathic pain generated by MS. Several US clinical trials have been performed, and the US Food and Drug Administration has approved phase 3 studies to evaluate CBME oral mucosal spray in patients with cancer. Obstacles remain to achieving full regulatory and legal approval for cannabis-based medicine in the United States. Eleven states have medical marijuana laws providing patients and caregivers a defense against prosecution; however, federal rulings have created gray areas in how far a practitioner may go to help a patient obtain cannabis.

Dr. Cliffored Gevirtz, (2007) points out that Cannabis has a very long history in medicine with early records going back 5000 years to China; it was then used to treat such conditions as malaria, constipation, and rheumatic pains.  Nonetheless, today there are two primary polarized camps fueling this debate.  One side preaches the evils of using this herb as medication and the other side extols the virtues of medical marijuana. 

Robson (2001) published his analysis of nine randomized controlled trials with a total of 222 adult patients.  These studies’ subjects had either cancer pain, chronic nonmalignant pain, or patients with postoperative pain.  In these trials oral THC 5-10 mg, an oral synthetic THC(NIB) 4 mg, and intramuscular levonantradol (Marinol) 1.5-3 mg.  These studies compared those interventions with oral codeine 60-120 mg and oral secobarbital (it has no analgesic properties but does have a sedative agent) 50mg.  Although the therapeutic benefits proved to be small and variable in these studies, they had clinical relevance because of the minimal side effects.

Gevirtz’s (2007) conclusions included noting a wide range of efficacy across various cannabis preparation but related poorly with efficacy compared with nonsteroidal anti-inflammatory drugs or other simple analgesics.  He also noted that increasing the cannabinoid dose to increase analgesia resulted in more adverse side effects.

There are also legality issues to consider because of the way in which the Drug Enforcement Agency (DEA) rates or “Schedules” drugs.  For Schedule I substances, the criteria that need to be considered are whether the substance has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision. While Schedule I drugs cannot be used medically, the law does allow supervised research.

For substances to be rated as Schedule II, the DEA considers its high potential for abuse, whether it has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions and whether abuse of the substances may lead to severe psychological or physical dependence.  While legal for medical use, doctors need to go through additional legal steps when prescribing these drugs.

A substance is placed on Schedule III based on its potential for abuse relative to substances in other schedules, whether it has a currently accepted medical use in treatment in the United States, and its relative potential to produce physical or psychological dependence is less.

What has been available for several years as a legitimate medication is Marinol (dronabinol), a synthetic THC (delta-9-tetrahydrocannabinol, the active psychoactive chemical in marijuana).  While marijuana is still listed as a Schedule I drug by the DEA and illegal for medical use, Marinol the synthetic form of THC has finally been reduced from Schedule II to a Schedule III Drug.

Marinol has been used in treating Glaucoma, people undergoing chemotherapy, and for people with AIDS.  Again sides are split on the effectiveness of this medication.  One side says Marinol works great therefore there is no need to legalize the medical use of marijuana.  The other side states that Marinol is not nearly as effective as smoked marijuana.

After working with many individuals who have used Marinol and also smoked marijuana, I see that both sides have good points.  For example, after helping some of my patients work through denial issues surrounding marijuana abuse, they become honest and share that the Marinol did work as well for controlling nausea or increasing appetite, but they didn’t get high.  On the other hand, several patients who needed help for nausea caused by chemotherapy treatment were not able to ingest the Marinol tablets and found smoking marijuana to be a better option for them.

There are also many risks associated with marijuana, especially smoked marijuana, which must be considered not only in terms of immediate adverse effects on the lung; e.g., bronchi and alveoli, but also long-term effects in people with chronic diseases and those with a poor immune status.  The major problems I have with someone smoking marijuana as a medicine is the inability to regulate the dosage and, even more important the delivery system.  The level of THC varies so greatly in the marijuana that is currently available, that coming up with a therapeutic dose is extremely difficult.  In addition, marijuana has other ingredients that may have problematic side effects.  Then there is the dangerous delivery system—the issue of smoking it.  The components of the smoke are hazardous, especially in the immuno-compromised patient.  No other medication we have is administered that way because of the potential dangers. 

Because of the lack of more positive research outcomes there has been minimal exploration of a safer delivery system for the active ingredient of marijuana (THC).  There have been suggestions that an aerosol delivery system for the THC or Marinol would eliminate the dosage and the unsafe smoking problems.  Why is this not being given due consideration?

One of the reasons may be that there is not enough profit for drug companies, but I believe the main reason is the stigma that has historically surrounded marijuana.  I think that marijuana is a serious drug of abuse that leads to dependency (addiction), but this is also true of many legal prescription medications.  For example Vicoden and OxyContin have both been increasingly abused in the past several years and Valium and Xanax have been a serious abuse problem for at least the past decade.

Another problem with medical marijuana is that it is often prescribed for conditions that may not be medially indicated.  In fact, several of my patients received medical marijuana prescriptions for stress management.  I am not aware of any legitimate research that indicates marijuana is a medically effective treatment for stress.  That is why more quality research needs to be undertaken to prove once and for all the legitimacy of using marijuana—or at least its active ingredient THC—to treat specific medical conditions.

Joy, Watson, & Benson, (1999) published their book Marijuana and medicine: Assessing the science base.  One major important finding of this book was that although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke.  In addition, plants contain a variable mixture of biologically-active compounds and cannot be expected to provide a precisely defined drug effect.  For those reasons, the book concludes that the future of cannabinoid drugs lies not in smoked marijuana, but in chemically-defined drugs that act on the cannabinoid systems that are a natural component of human physiology.  Until such drugs can be developed and made available for medical use, the report recommends interim solutions.  The development of these appropriate drugs depends upon thorough double-blind clinical trials.

I understand this is a very controversial issue.  While I am not in favor of legalizing street drugs I do advocate utilizing a potentially effective medication after it has undergone the same level of testing as the other medications we currently use.  Like Gevirtz (2007) I do not believe that there is enough valid evidence to support the introduction of cannabinoids into widespread clinical practice for pain management.  I also believe that in addition to verifying the effectiveness; the delivery system and dosage problems need to be resolved before I would feel comfortable endorsing the use of medicinal marijuana for any of my patients. 

Bibliography

Barnes MP. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother. 2006;7:607-615.

Gevirtz, C.,  (2007).  An emerging therapy: The future role of cannabinoids in pain management.  Topics In Pain Management, Vol. 22, #8, pp. 1-5.

Holdcroft, A., Maze, M., & Dore, C. B., (2006).  A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for post-operative pain management.  Journal of Anesthesiology, Vol. 104; pp. 1040-1046

Joy, J., Watson, S. J., & Benson, J. A.,  Editors, (1999).  Marijuana and medicine: Assessing the science base.  Washington; DC.  National Academies Press

Mackie K, Huestis MA, Ratcliffe S, Mead AP. Cannabinoids -- a new class of analgesics. Presentation of the 23rd Annual Meeting of the American Academy of Pain Medicine; February 8, 2007; New Orleans, Louisiana.

Pertwee, R. G.,  (1999).  Cannabis and cannabinoids: Pharmacology and rationale for clinical use.  Rorsch Komplementarmed, Vol. 6, (suppl 3): pp. 12-15.

Reynolds, J. R.,  (2005) Therapeutical uses and toxic effects of Cannabis indica. Lancet, 1890; i: pp. 637-638.

Robson, P.,  (2001).  Therapeutic aspects of cannabis and cannabinoids.  British Journal of Psychiatry; #178: pp. 107-115.

Webster, L. R. (2008) Opioid and Nonopioid Therapies for the Management of Pain. Medscape.com (http://cme.medscape.com/viewprogram/6856_pnt).