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Introduction:

Cannabis as Alternative Medicine

Cannabis has been used for millennia in cultures worldwide as a medicinal plant. Given the
numerous references in ancient texts, at one-time cannabis was as conventional as Penicillin. It’s
only relatively recently that Western medicine has eclipsed herbal treatments, cannabis among
them, and consigned them to the alternative bucket, in the esteemed company of acupuncture and
homeopathy.

An American Tradition
Cannabis wasn’t always considered alternative medicine on American soil. It was widely used by
native tribes from coast to coast. Even George Washington grew cannabis and noted its
medicinal qualities in agricultural ledgers.

Today, cannabis is regaining respect for its healing chops. It’s now widely used to treat pain,
nausea, anxiety, depression, muscle spasms, and seizures. Those with multiple sclerosis,
Parkinson’s disease, and epilepsy all report therapeutic effects. Israeli researchers are exploring
the potential of cannabis to treat traumatic brain injuries; while a Harvard study found cannabis
helped stabilize the brains of people who suffer from bipolar disorder. Other studies are
investigating the effects of cannabis on Alzheimer’s disease and various forms of cancer.

How is it possible for one plant to treat such a diverse range of conditions? As it turns out,
cannabis is a veritable pharmacy of beneficial chemical compounds. The plant is comprised of
over 100 cannabinoids, the most famous of which are tetrahydrocannabinol (THC) and
cannabidiol (CBD). The therapeutic qualities of these phytonutrients have been well
documented, and more are emerging every day.

Conversely, researchers are only beginning to study the healing effects of terpenes. Specific
concentrations of terpenes are what gives each cannabis strain its distinctive taste, smell, and
unique bundle of therapeutic properties—antidepressant, anti-inflammatory, antioxidant,
antifungal, anti-anxiety, among them.
There is still much to learn about how cannabinoids and terpenes do all the amazing things they
do. Evidence suggests that we may only have uncovered the tip of the iceberg. As new research
catches up to ancient knowledge, cannabis is returning to its mainstream status. The wheel turns.

while traveling in China in 1971, two-time Pulitzer Prize-winning journalist James Reston
underwent an emergency appendectomy, after which Chinese medical personnel treated his
pain with acupuncture. His description of the experience in the pages of the New York Times
brought the practice of traditional Chinese medicine front and center.

Two years later, Lewis Thomas, then president of Memorial Sloan-Kettering Cancer Center,
delivered an address in which he said, “These are bad times for reason, all around. Suddenly,
all of the major ills are being coped with by acupuncture. If not acupuncture, it is apricot pits.”
Thomas was referring to laetrile, a compound extracted from the pits of apricots and bitter
almonds, one of the most sought-after alternative treatments for cancer at the time, but one
whose effectiveness had been the topic of bitter controversy for years. Banned since 1963 in
the U.S., laetrile is reported to still be readily available in the Bahamas and Mexico and is sold

.
And the examples don’t end there. Lots of ballyhoo, head-scratching, and accusations of

quackery attended growing patient demand for alternative treatments, hyped in the popular press

as cures that were “natural” and based on millennia-old medical traditions practiced in places

such as China and India.

In 1999, in response to a growing outcry for some kind of evidence-based scientific analysis of

the safety and efficacy of this blizzard of nonconventional treatments, the National Institutes of

Health, then under the direction of Harold Varmus, established the National Center for

Complementary and Alternative Medicine (NCCAM). Since its founding, NCCAM has funded

basic and clinical research at institutions around the world on plant and animal products such as

acai, black cohosh, gingko biloba, and shark cartilage, as well as on the therapeutic value of

treatments including acupuncture, yoga, massage, reiki, and meditation.

Almost 40 percent of US adults and 12 percent of US children have used complementary or

alternative therapies, according to a 2007 survey by NCCAM, and much of what was once

considered “alternative,” including acupuncture, is now part of more-holistic regimens offered at

40 percent of US hospitals, including Memorial Sloan-Kettering Cancer Center. According to a

2010 survey by the American Hospital Association and the Samueli Institute, a nonprofit center

for the study of wellness and healing, this trend is driven by patients demanding alternative or

complementary treatment options for conditions that are difficult to manage or cure, such as

diabetes, chronic pain, and cancer. Most physicians have l​ukewarmly embraced such therapies,

often because they feel that patients will desert conventional therapy out of desperation if they

are not offered a wider range of treatment options.

Researchers who study the scientific validity of non conventional treatments rarely see them as

stand-alone remedies, preferring to call the union of conventional and nonconventional

“integrated therapy.”

The Scientist​ staff asked experts about the scientific evidence for a number of treatments that

may be on the verge of becoming incorporated into integrated therapies, from acupuncture and

probiotics to marijuana and psychedelics. We sought to highlight the data that either supports or

contravenes the effectiveness of these alternative therapies. As with most health interventions,

we uncovered both positive and negative aspects of these treatments for which patients are

clamoring and physicians are demanding evidence.

Facts about the benefits of medical marijuana are sparse, hampered by the politics and

regulatory difficulties of doing such research.

Marijuana (​Cannabis ​sp.) has been used as a medicine for more than 4,000 years. But in the eyes of the US federal

government, cannabis is an illegal drug that has no place in the clinic. Biomedical researchers who would like to

study cannabis in a medical setting are frustrated by the challenges of obtaining government clearance and funding.

But some data pointing to medical benefits of smoking marijuana do exist.

In 1970, the US Congress voted to classify cannabis under Schedule I of the Controlled Substances Act. Marijuana

joined heroin, LSD, and peyote on Schedule I, and according to the Act, it—along with all other Schedule I
drugs—has a high potential for abuse, lacks safety, and has “no currently accepted medical use in treatment in the

United States.”

Since then, 16 US states and the District of Columbia have legalized the use of medicinal

cannabis for a variety of indications, from chronic pain to cancer- and HIV-related appetite and

weight loss, nausea, and vomiting. But despite the recent wave of state-level legalization, and the

enactment of similar laws in Canada and elsewhere around the globe, the US federal government

still classifies marijuana as a Schedule I drug, a designation that makes studying the medical

effects of the drug in the U.S. extremely difficult (requiring approval from the Drug Enforcement

Administration in addition to the Department of Health and Human Services (HHS)). Therefore,

it has been far more common (and easier) to get funding and clearance to study the negative

impacts of marijuana as a substance of abuse than to investigate its positive effects as a

therapeutic agent.

Nonetheless, some researchers have braved the bureaucratic obstacles to conduct a handful of

randomized, placebo-controlled trials that point to benefits of smoking cannabis, though they

acknowledge that smoking the plant comes with its own risks and drawbacks. A more extensive

body of literature involves molecular components, extracts, or synthetic forms of marijuana,

simply because studying these non-Schedule I substances is less fraught with regulatory

obstacles than is studying the whole plant.

The strongest evidence of smoked marijuana’s benefit exists in patients who experience chronic

pain. With funding from the University of California Center for Medicinal Cannabis Research

(CMCR), researchers published studies in 2007, 2008, and 2009 that all suggested smoked

cannabis possessed analgesic properties. A study published in 2007, for example, noted that HIV

patients experiencing neurological pain, or neuropathy—a general name for burning pain,

hypersensitivity to light touch, and other uncomfortable symptoms—experienced a dulling of

that pain when they smoked a cannabis cigarette three times a day for 5 days.

Psychiatrist Igor Grant, director of the center and an HIV/AIDS researcher at the University of

California, San Diego, says that patients suffering from neuropathy in particular seem to find

relief in cannabis. “We don’t have terrific agents to treat it. There are agents [such as

antiepileptics and antidepressants] and they are modestly effective in many people,” Grant says.

“The bottom line is that [cannabis] seems to work, and the effects are comparable in strength to

traditional agents.”

Other studies from the CMCR have probed new conditions the plant might be used to treat. For

example, UC San Diego researchers reported in 2008 that smoked marijuana has the potential to

reduce muscle spasticity in multiple sclerosis (MS) patients. That finding was bolstered by a

randomized, double-blind, placebo-controlled study published last year on the liquid marijuana

extract Sativex, which is approved for use in some European countries, Canada, and New

Zealand. The results of that trial, conducted by European researchers, indicated that a 4-week

course of Sativex, an oral spray that contains the cannabinoids cannabidiol (CBD) and delta-9

tetrahydrocannabinol (THC), was safe and effective at reducing spasticity in many MS patients.
US researchers are completing Phase III trials of Sativex for the treatment of pain associated

with cancer, and Otsuka Pharmaceutical, the US licensing partner of UK drugmaker GW

Pharmaceuticals, hopes to gain FDA approval soon.

Aside from the relative logistical ease of studying constituents, extracts, or synthetics due to the

fact that they do not run afoul of the Controlled Substances Act, these compounds stimulate the

endocannabinoid system, the body’s homegrown constellation of receptors that interact with the

active components of cannabis in a more tractable way than does smoked cannabis. “Harnessing

that system with medications is a potentially new avenue for therapeutics,” says Mark Ware,

McGill University neurologist and pain physician.

For example, Marinol is a synthetic THC drug that is used by chemotherapy patients

experiencing nausea and vomiting or AIDS patients who are rapidly losing weight. It is the only

FDA-approved synthetic cannabinoid, and offers an alternative to conventional therapies for

these patients, though results have been mixed when comparing its effects to those of smoked

cannabis, with the herbal version usually outperforming the synthetic.

This highlights one problem with going the synthetic route in the eyes of some cannabis

researchers. “We shouldn’t forget that the herbal product contains multiple other constituents

which may add to the effects of any one single agent,” says Ware. Also problematic are isolated

cannabinoids’ tendency to be rapidly broken down in the liver and the difficulty in determining

optimal doses.

As the political and social storm around medical cannabis continues to brew, most researchers

who have seriously tested the drug’s therapeutic properties lament their inability to freely study it

in a medical context. “The [cannabis] laws date to a time when what we knew about marijuana

was voodoo,” says Mayo Clinic psychiatrist Michael Bostwick. “[The drug] can’t be applied to

humans and to therapeutics because the laws don’t permit it to be done. The whole attitude

towards medical marijuana is just irrational.”

For its part, the NIH claims that studying smoked marijuana is fair game. “Research projects

seeking to determine the therapeutic potential of smoked marijuana are considered under the

same criteria as any other project submitted for NIH funding,” the agency wrote in an e-mail to

The Scientist​. “Investigator-initiated applications for NIH funding are evaluated by peer-review

groups composed of scientists from outside the NIH. The peer-review group evaluates the

scientific and technical merit of the proposed research.” That said, the NIH’s Research Portfolio

online Reporting Tools (RePORT) database lists many more active projects focusing on

molecular components of cannabis or marijuana as a harmful drug than it does projects seeking

to probe the potential medical benefits of smoking cannabis. Still, officials at the HHS also claim

that the US government is game to fund studies of medical marijuana. “We’re very open to

people submitting applications and trying to make [evaluating medical marijuana study

proposals] a transparent and efficient process,” says Sarah Wattenberg, senior advisor for

substance abuse policy at HHS. “In order for us to move this forward at all, we have to take the

politics and stigma away, deal with it as a therapeutic class, and give people what science there

is,” says Ware.

Particularly vexing to Ware is that so many people all over the world are using marijuana either
recreationally or for the treatment of some ailment, legally or more often illegally, while science
is forced to sit idly by and miss out on all that potential data. “We have so many people who are
already doing the drug in one form or another in some sort of legal framework, but they’re not
being involved in any type of research,” he says. “There’s kind of a huge natural experiment
going on right now, and we’re not learning from it.”

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