Medical marijuana use has a history stretching back thousands of years. In prebiblical times, the plant was used as medicinal tea in China, a stress antidote in India and a pain- reliever for earaches, childbirth and more throughout Asia, the Middle East and Africa.

In recent decades, medical researchers have investigated marijuana’s effects on various kinds of pain -- from damaged nerves in people with HIV, diabetes and spinal cord injury; from cancer; and from multiple sclerosis. Marijuana has also been hypothesized to help with nausea induced by chemotherapy and antiretroviral therapy, and with severe loss of appetite as seen in people with the AIDS wasting syndrome.

The weed’s actions are due to the active ingredients tetrahydrocannabinol (THC) and some 60 other cannabinoids, which mimic the action of chemicals -- known as endogenous cannabinoids -- that exist naturally in the brain. Those cannabinoids activate receptors in our nerves, triggering physiological responses.

A legal prescription form of THC (Marinol) exists, yet researchers say it’s far from a perfect drug. Taken orally, its absorption is highly variable and unpredictable and often delayed, says Dr. Igor Grant, a UC San Diego psychiatrist who directs the university’s Center for Medicinal Cannabis Research. “Smoking is a very efficient way to deliver THC,” he says.

As a result of its federally illegal status, medicinal use of marijuana is restricted to carefully vetted clinical research studies or to patients in states such as California that have passed laws to allow for personal medical use. Research on the medicinal use of marijuana relies on government-issued marijuana cigarettes, which come in different strengths and are supplied by the National Institute on Drug Abuse.

The UC Center for Medicinal Cannabis Research in San Diego helps coordinate clinical studies to investigate the safety and effectiveness of marijuana. Here’s what they’ve found.

Neuropathic pain

Recent research suggests that marijuana can assuage this chronic-pain syndrome in which burning sensations occur and simple touch can feel like hurt. It is unaffected by aspirin-like drugs and fairly resistant to stronger analgesics such as opiates.

In a 2007 study on neuropathic pain related to HIV infection, 50 patients smoked marijuana cigarettes three times a day or marijuana cigarettes from which active ingredients had been extracted. Subjects then rated their pain on a scale ranging from “no pain” to “worst pain imaginable.” The results, published in the journal Neurology, showed a 34% reduction in ratings of pain in the marijuana group compared with 17% in the placebo group over five days of treatment.

Another study in 44 patients reported in June in the Journal of Pain found that marijuana alleviated neuropathic pain arising from a variety of conditions, including spinal-cord injury and diabetes. Participants smoked marijuana on a set schedule -- first two puffs, then three puffs an hour later, then four puffs an hour after that -- from a single cigarette containing either 0%, 3.5%, or 7% THC. Average pain ratings before smoking were 55 on a 100-point scale and decreased by 46% in both treatment groups and by 27% in the placebo group one hour after the last puff.

Analgesic drugs are often tested against experimentally induced pain. Such studies have been conducted for marijuana too. In one 2007 report in the journal Anesthesiology, 15 healthy volunteers received skin injections with capsaicin -- the chemical behind that fiery spice in chile peppers -- and then smoked different-strength marijuana cigarettes. The medium dose, with a 4% THC concentration, lessened the burning pain.

These three pain studies all concluded that smoked marijuana can bring relief to sufferers of neuropathic pain comparable to other analgesic drugs. It is not a cure, Grant says: “It’s like other pain medicines, you have to keep taking it.”

Study subjects did feel high, an effect that varied among individuals. Marijuana also affected thinking, shown as problems with tasks of memory and complicated reasoning after the strongest marijuana cigarettes were used. Potentially problematic, these effects were tolerated by subjects -- no one opted out of the study because they couldn’t think straight.

Grant says it’s important to have a choice of treatments because not everyone responds to or can tolerate the available drugs. Antidepressants are used for neuropathic pain but cause dry mouth, constipation and urinary problems, and must be avoided by people with conditions such as glaucoma. Others can’t take aspirin-like drugs. “Having an alternative compound is always good,” Grant says.

Multiple sclerosis

Patients with multiple sclerosis suffer muscle spasms, pain and tremor. Anecdotal reports suggest that marijuana may be helpful, but controlled studies are few. One, presented at an April meeting, had 51 multiple sclerosis patients smoke 0% or 4% THC marijuana cigarettes daily for three days. Intensity of spasms was reduced by 32% and pain ratings by 50% after smoking marijuana, compared with 2% and 22% reductions after placebo cigarettes. Five subjects withdrew, citing side effects: feeling too high, dizzy or fatigued.

Other studies in patients with multiple sclerosis used a cannabis extract that can be taken orally. In a 2007 European Journal of Neurology study, nearly half of 184 patients experienced at least 30% improvement in muscle spasms.

But a 2004 Neurology paper showed no reduction in objective measures of arm tremor with cannabis extract, although five subjects out of 13 reported feeling improvement. This might have resulted from mood-altering effects of the drug or from some aspect of tremor not measured.

Nausea

A 2008 review published in the European Journal of Cancer Care analyzed 30 clinical studies using cannabinoid drugs synthesized in the lab and concluded that they were better than standard antinausea drugs in alleviating the nausea and vomiting that accompanies chemotherapy. One such drug is Marinol, a THC preparation approved by the Food and Drug Administration for precisely this purpose.

Survey studies suggest that some people with HIV smoke marijuana to counteract nausea caused by antiretroviral therapy. Researchers at the UC Center for Medicinal Cannabis Research have tried to study the effect of smoked marijuana on nausea and vomiting in patients undergoing chemotherapy but have struggled to enroll enough subjects, Grant says.

Bruce Mirken, director of communications for the Marijuana Policy Project -- a group that lobbies for the decriminalization of marijuana -- says he is all for research on the chemical components in marijuana with the goal of making more-purified and perhaps more-targeted drugs that do not deliver a “high,” but does not see “criminalizing use of that plant by people who are ill when you are making its main psychoactive ingredient legal in the form of a very expensive pill.”

Tom Riley, a spokesman for the White House Office of National Drug Control Policy, says marijuana advocates are seeking a free pass. “They want to be exempted from the regular [drug] approval process,” he says.