Evidence for medical marijuana: The grass isn't always greener

By John Murphy, MDLinx
Published January 6, 2016

Key Takeaways

The world has gone to pot—in more ways than one. In 1996, California became the first state to legalize medical marijuana. Since then, 22 other states, as well as Washington DC and Guam, have allowed its use in one form or another.

States vary in the type and amount of medical marijuana allowed and the indications for approved use. Some states, such as Massachusetts, permit the medicinal use of marijuana for only a handful of medical conditions. Other states, such as Illinois and New Hampshire, allow it as treatment for dozens of indications.

Unfortunately, reliable medical research hasn’t caught up to this legal progressiveness. Prescribers are caught in the middle as patients are increasingly asking about marijuana’s medical use, yet doctors aren’t armed with enough knowledge to provide proven advice.

Thus, the evidence of the benefits and the drawbacks of medical marijuana need to be further understood. Yet few rigorous, randomized clinical trials—the conventional proving ground for prescription medications—have been undertaken for medical marijuana.

To that end, a research team led by Penny F. Whiting, PhD, of the University of Bristol, Bristol, United Kingdom, scoured the literature by searching various databases for randomized clinical trials of cannabinoids for a variety of indications. The researchers identified 79 trials (including 6,462 participants) that met the rigorous criteria to be included in their review and meta-analysis. Few of the studies they found had evidence they deemed to be of even moderate quality; most of the studies were judged to be of low quality. Their results were published in an article in the June 23/30, 2015, issue of JAMA.

In short, the researchers concluded that most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies.

For specific medical conditions, here’s the evidence they found:

Indications with moderate-quality evidence

  • Chronic pain: The JAMA meta-analysis included 28 studies that assessed cannabinoids for a variety of chronic pain conditions—neuropathic pain, cancer pain, diabetic peripheral neuropathy, fibromyalgia, HIV-associated sensory neuropathy, among others. Overall, results showed that the number of patients who had a reduction in pain of at least 30% was greater with cannabinoids than with placebo.
  • Spasticity: Fourteen studies that assessed spasticity due to multiple sclerosis or paraplegia were included. Studies generally suggested that cannabinoids lessened spasticity—7 trials showed an average reduction in the Ashworth spasticity scale of -0.36—but results failed to reach statistical significance in most studies.

Indications with low-quality evidence

  • Nausea and vomiting due to chemotherapy: In 3 of the 28 trials included in the meta-analysis, cannabinoids showed a complete response in relieving nausea and vomiting in 47% of patients compared with 27% of patients on placebo. All trials showed positive results, but these didn’t reach statistical significance in all studies.
  • Appetite stimulation in patients with HIV/AIDs: In popular culture, smoking marijuana is believed to cause “the munchies.” Because people diagnosed with HIV and AIDS can lose their appetite, researchers have investigated medical marijuana for stimulating hunger in these patients. The meta-analysis included 4 studies, which showed limited evidence of stimulated appetite and weight gain; however, most outcomes failed to reach statistical significance.
  • Depression: The investigators could find no studies on use of cannabinoids for depression that met their inclusion criteria; however, 5 studies for other indications also reported depression outcomes. Nevertheless, most of these studies found no difference between cannabinoids and placebo in improving depression outcomes.
  • Sleep disorders: Drowsiness from smoking marijuana is another notion in popular culture. The researchers included 2 studies in their meta-analysis that evaluated cannabinoids for treating sleep problems. In addition, 19 placebo-controlled studies for other indications also evaluated sleep as an outcome. Overall, cannabinoids were associated with a greater average improvement in sleep quality (in 8 trials) and reducing sleep disturbance (in 3 trials).
  • Anxiety disorders: One small trial reported that cannabinoids, when compared with placebo, were associated with greater improvement on an anxiety scale during a simulated public speaking test. In addition, four studies that evaluated cannabinoids for chronic pain also included anxiety outcomes, and these suggested cannabinoids offered a greater benefit to patients with anxiety disorders than placebo.
  • Psychosis: Two trials included in the JAMA meta-analysis found no difference in mental health outcomes between cannabinoid and placebo treatment groups,
  • Glaucoma: The meta-analysis included only 1 small trial (of 6 patients) that evaluated cannabinoids for lowering intraocular pressure due to glaucoma. This trial found no difference between cannabinoids and placebo for glaucoma.
  • Tourette syndrome: Two small placebo-controlled studies (a total of 36 participants with Tourette syndrome) indicated that cannabinoids may significantly lessen severity of tics.

The studies included in this meta-analysis tested a variety of different cannabinoid preparations dosed in various routes of administration, including capsules, smoked marijuana, vaporized marijuana, oromucosal spray, and intramuscular injection. Bear in mind that marijuana has no single active ingredient, but is a complex of more than 400 compounds including more than 60 pharmacologic cannabinoids—the primary ones being tetrahydrocannabinol (THC) and cannabidiol (CBD). Only 2 cannabinoids—dronabinol and nabilone—are available as FDA-approved prescription medications.

Adverse effects

While the efficacy of medical marijuana requires further robust clinical trials, the adverse short- and long-term effects are much better known, the authors wrote. Acute effects of marijuana include impaired short-term memory, motor coordination, and judgment. Paranoia and psychotic disorder, although rare, may also occur in high doses. Long-term effects of frequent marijuana use include structural brain changes, chronic bronchitis, and increased rates of respiratory tract infections and pneumonia. Also, marijuana is potentially addictive in about 1 in 10 users.

“Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, double-blind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety,” wrote Deepak Cyril D’Souza, MBBS, MD, and Mohini Ranganathan, MD, of the Yale University School of Medicine, New Haven, CT, in a JAMA editorial accompanying the meta-analysis. “Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process.”

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