Marijuana as Medicine

Nearly half the country has so far made it legal. Does it work?

Medical marijuana is quickly becoming a popular treatment for hundreds of thousands of patients for whom conventional treatments have failed.

 

By Steve Sternberg

By 2013, Liz Gorman had lost hope. Her daughter Maddie, then 6, suffered from relentless seizures, untamed by 13 medications and even brain surgery. Maddie could barely fall and stay asleep, much less learn to read. Even waking up triggered seizures. Desperate, Gorman began weighing a treatment – a cannabis extract called Charlotte's Web – she'd never thought she would try. "I'm a conservative Republican, the wife of a major in the Marine Corps," she says. "It never dawned on me that this was the way to fix my child."

Moreover, getting access to Charlotte's Web would mean leaving her husband and home in Raleigh, North Carolina, and moving Maddie to Colorado, where the extract is made and where in 2012 medical marijuana was legalized. In the end, willing to do anything to help her daughter, Gorman relocated to Colorado Springs in December 2013. She now gives Maddie one drop of Charlotte's Web oil twice each day and marvels at her improvement. Her seizure rate is down by 95 percent. "I hate to use the word miraculous," she says, "but for us, it really has been."

Federal law says marijuana is a controlled substance with a high potential for abuse and "no currently accepted medical use." But that hasn't stopped 23 states and the District of Columbia from legalizing varieties of cannabis – a genus that includes marijuana and hemp, which has therapeutic but not mind-altering properties.

States have approved cannabis use for conditions as wildly dissimilar as epilepsy, chronic pain, the loss of appetite and nausea caused by chemotherapy, muscle spasticity associated with multiple sclerosis, diabetes, glaucoma and post-traumatic stress disorder. In some states, retailers are cautiously stocking their shelves with cannabis-based edibles, oils, mists, lotions, lip balms and flower buds.

They're moving cautiously because federal law trumps state law, and while some members of Congress want to prevent the government from intervening, there's been no consensus on action yet. "There's legitimate fear in the marketplace that, if we go in and set up shop, we'll have the police on our backs," says Douglas A. Berman, professor of law at Ohio State University.

In March, several bills were introduced, the most ambitious a measure that would let states legalize marijuana for medical use without federal interference. Another bill would exclude Charlotte's Web from the list of controlled substances. Other measures would limit federal prosecutors' power to go after growers, vendors and users who obey state laws.

Meantime, as people like Gorman testify to the plant's effects, medical marijuana is rapidly becoming a go-to treatment for hundreds of thousands of patients for whom conventional treatments have failed. This is true despite the fact that research into the plant's benefits is worryingly thin. A sweeping review of the research done so far, published in the Journal of the American Medical Association in June, found that most studies have produced, at best, only "moderately" trustworthy evidence of effectiveness, mostly in patients undergoing cancer chemotherapy, people suffering chronic pain, and multiple sclerosis patients with pain and spasticity.

The evidence was "poor" for many state-approved indications, such as hepatitis C, Crohn's disease, Parkinson's disease and Tourette syndrome, wrote psychiatrists Deepak Cyril D'Souza and Mohini Ranganathan of the Yale University School of Medicine in an accompanying editorial. Research on seizures is going on now. On the other hand, cannabis contains a potential pharmacopeia of more than 80 chemicals called cannabinoids and approximately 400 other compounds.

"I do believe if we did the appropriate research, we would find some of those compounds have true medicinal value," says Otis Brawley, chief medical officer of the American Cancer Society.
The cannabinoid responsible for marijuana's mind-altering properties, delta-9-tetrahydrocannabinol or THC, was identified in the early 1960s along with the active ingredient in Charlotte's Web, cannabidiol, which lacks THC's trippy high.

One explanation for medical marijuana's broad biological activity is that humans, like all other creatures, have innate cannabinoids that bind to receptors in the brain and immune system and play a critical role in growth and development, scientists say. Research in animals shows that if you block cannabinoid receptors in infancy, the animals will stop eating and die.

The receptors' location may offer clues to cannabinoids' perceived medical effects. One set of receptors is concentrated in nerve centers linked to pain perception, for example; a second set, mainly found in the immune system, may account for cannabis' potent – and well-established – anti-inflammatory properties. Scientists have found that cannabinoids act as a nervous system dimmer switch, slowing or blocking signals between nerve cells.

High concentrations of signal-blocking cannabinoid receptors throughout the brain may explain why cannabinoids appear to quell seizures. Receptors are similarly dense in regions that control movement, promote appetite and combat nausea, which may explain why marijuana seems to relieve muscle spasticity and boost appetite. Although cannabis has many side effects – dry mouth, bloodshot eyes, inceased appetite, diminished short-term memory, anxiety and impaired reaction time among them – no fatal overdose has ever been reported.

That's likely due to the relative absence of cannabinoid receptors in the brain stem, the region that controls heart rate and breathing.
Some researchers believe that cannabinoids may actually treat cancer itself. In the lab, they stop cells from dividing and slow the spread of cancer cells into nearby tissues. And researchers in Spain and England have shown that cannabinoids can shrink brain tumors in animals.

"Our animal work is very convincing indeed," says Stephen Wright, chief medical officer of GW Pharmaceuticals, a British firm that is developing cannabis-derived drugs. The company is now studying a drug in patients with recurrent brain cancer, Wright says, with results due next year.

Beyond the plant extracts, two drugs that are synthetic versions of THC, Marinol and Cesamet, are available by prescription across the U.S. Both were approved in 1985 to relieve nausea and vomiting in cancer patients. Marinol also has been shown to combat weight loss in people with HIV/AIDS. In addition, GW Pharmaceuticals has three pharmaceutical-grade cannabis medicines, including one, still unnamed, that is being tested in patients with Type 2 diabetes.

Sativex, a mix of cannabidiol and THC, is approved in 28 countries for relieving spasticity and is being tested in the U.S. for its ability to relieve cancer pain.
The third drug, Epidiolex, made of cannabidiol only, is being tested in children with severe epilepsy whose seizures haven't responded to other drugs.

Preliminary results in more than 130 children revealed that after 24 weeks of treatment, their average number of seizures had fallen by 45 percent, says neurologist Orrin Devinsky, director of the NYU Langone Comprehensive Epilepsy Center, who is leading the trial. In Colorado, neurologist Edward Maa, chief of the Comprehensive Epilepsy Program at Denver Health Medical Center, is taking advantage of the community using Charlotte's Web to closely monitor the experience of 150 seizure patients.

Maddie, now 8, is rapidly making the headway she couldn't when constantly having seizures. "She knows her ABCs now. She knows her colors and her shapes," says Gorman. "We plan to begin working on sight-words this summer."