3264. Earliest Evidence for Cannabis Use Discovered in Ancient Tombs

By Michele Donahue, National Geographic, June 12, 2019

2,500-year-old burials at Jirzankal Cemetery in western China feature wooden braziers that burned cannabis plants containing an unusually high level of the psychoactive chemical THC. Photo:
Wu Xinhua.

The earliest direct evidence for human consumption of cannabis as a drug has been discovered in a 2,500-year-old cemetery in Central Asia, according to a research paper published today in in the journal Science Advances.

While cannabis plants and seeds have been identified at other archaeological sites from the same general region and time period—including a cannabis ‘burial shroud’ discovered in 2016—it’s been unclear in each context whether the versatile plant was used for psychoactive reasons or for other ritual purposes.

An international team of researchers analyzed the interiors and contents of 10 wooden bowls excavated from burials at Jirzankal Cemetery, a site on the Pamir Plateau in what is now far-western China. The bowls contained small stones that had been exposed to high heat, and archaeologists identified them as braziers for burning incense or other plant matter.

When chemical analysis of the braziers revealed that nine of the ten once contained cannabis, the researchers compared the chemical signature of the samples against those of cannabis plants discovered 1,000 miles to the east at Jiayi Cemetery, in burials dating from the eighth to the sixth century B.C.

They saw that the Jirzankal cannabis had something the Jiayi hemp did not: Molecular remnants of tetrahydrocannabinol, or THC—the chemical responsible for cannabis’ psychoactive effects. The strain of cannabis found at Jiayi does not contain THC, and would have been primarily been used as a source of fiber for clothing and rope, as well as nutrient-rich oilseed.

The Jirzankal cannabis features higher levels of mind-altering compounds than have yet been found at any ancient site, suggesting that people could have been intentionally cultivating certain strains of cannabis for a potent high, or selecting wild plants known to produce that effect.

Cannabis is known for its “plasticity,” or ability for new generations of plants to express different characteristics from earlier generations depending on exposure to environmental factors such as sunlight, temperature, and altitude. Wild strains of cannabis growing at higher altitudes, for instance, can have a higher THC content.

While the researchers are unable to determine the actual origin of the cannabis used in the Jirzankal burials, they suggest that Jirzankal’s elevation some 10,000 feet on the Pamir Plateau may have put people in close proximity to wild strains with higher THC content—or that the cemetery could have been sited at that elevation for ease of access to desirable strains.
 
According to Spengler, this new study demonstrates that already 2,500 years ago, humans were potentially targeting specific plants for their chemical production

Robert Spengler, director of paleoethnobotany laboratories at the Max Planck Institute for the Science of Human History and study co-author, says that the constant stream of people moving across the Pamir Plateau—an important crossroads connecting Central Asia and China with southwest Asia—could have resulted in the hybridization of local cannabis strains with those from other areas. While hybridization is another factor known to increase psychoactive cannabis strains’ THC potency, the question of whether it was intentional, or just by happy accident, is also still unclear.

“It’s a wonderful example of how closely intertwined humans are and have been with the biotic world around them, and that they impose evolutionary pressures on the plants around them,” he says.

The discovery at Jirzankal also provides the first direct evidence that humans inhaled combusted cannabis plants in order to obtain its psychoactive effects. No evidence of smoking pipes or similar apparatus has been found in Asia before contact with the New World in the modern era, but the inhalation of cannabis smoke from a heat source is described by the fifth-century B.C. Greek historian Herodotus, who described in his Histories how the Scythians, a nomadic tribe living on the Caspian Steppe, purified themselves with cannabis smoke after burying their dead: “The Scythians then take the seed of this hemp and, crawling in under the mats, throw it on the red-hot stones, where it smolders and sends forth such fumes that no Greek vapor-bath could surpass it. The Scythians howl in their joy at the vapor-bath."

Herodotus also notes that the cannabis plant “grows both of itself and having been sown,” which University of North Carolina classics expert Emily Baragwanath says is usually interpreted as meaning the plant was cultivated—lending credence to the researcher’s ideas about purposeful cannabis hybridization.

"People have been skeptical of Herodotus’ ethnographies of foreign peoples," she adds, "but as archaeology looks closer, it keeps finding affinities between the real world and what’s in the Histories."

Mark Merlin, an ethnobotanist and cannabis historian at the University of Hawaii at Manoa, says the wide diversity in cannabis around the world today is a testament to how long people have been involved with the plant and harnessed its many uses. “It’s a real indication of how long humans have been manipulating cannabis,” he says.

2245. Marijuana-Based Drug Found to Reduce Epileptic Seizures

By Andrew Pollack, The New York Times, March 14, 2016

Aaron Klepinger says a daily dose of liquid marijuana extract helps prevent his son, Hunter, from suffering severe seizures. CBS News. 

An experimental drug derived from marijuana has succeeded in reducing epileptic seizures in its first major clinical trial, the product’s developer announced on Monday, a finding that could lend credence to the medical marijuana movement.

The developer, GW Pharmaceuticals, said the drug, Epidiolex, achieved the main goal of the trial, reducing convulsive seizures when compared with a placebo in patients with Dravet syndrome, a rare form of epilepsy. GW shares more than doubled on Monday.

If Epidiolex wins regulatory approval, it would be the first prescription drug in the United States that is extracted from marijuana. The drug is a liquid containing cannabidiol, a component of marijuana that does not make people high.

As many as 30 percent of the nearly 500,000 American children with epilepsy are not sufficiently helped by existing drugs, according to GW. Parents of some of these children have been flocking to try marijuana extracts, prepared by medical marijuana dispensaries.

A number of states, in response to pressure from these parents, have passed or considered legislation to make it easier to obtain marijuana-based products. And some families have become “marijuana refugees,” moving to Colorado where it has been easier to obtain a particular extract, known as Charlotte’s Web, after the girl who first used it to control seizures.

Hundreds of other children and young adults have been using Epidiolex outside of clinical trials, under programs that allow desperate patients to use experimental drugs.

While many parents have reported significant reductions in seizures, experts have been cautious about anecdotal reports, saying that such treatments needed to be compared with a placebo to make sure they work. As such, the results from the GW trial have been closely watched.

“I’m very proud and happy about this study because it is science — we did things the way they should be done,” the study’s lead investigator, Dr. Orrin Devinsky of the Comprehensive Epilepsy Center at New York University Langone Medical Center, said in an interview. “I would strongly advocate that in the United States we need to do systematic assessments of medical marijuana.”

The study involved 120 patients with an average age of 10 and an average frequency of 13 convulsive seizures a month at the start of the study, despite taking an average of three other drugs. Half of the children were randomly assigned to take the drug and the other half the placebo, in addition to the epilepsy medicines they were already taking.

The company said that for the patients who received Epidiolex, the frequency of convulsive seizures fell by 39 percent during the 14-week treatment period, compared with a four-week period just before the treatment started. For those getting the placebo, the reduction was 13 percent. The difference between the two groups was statistically significant.

Eight patients getting Epidiolex and one getting the placebo withdrew from the trial because of side effects. Major side effects included drowsiness, diarrhea, decreased appetite, fatigue, fever, vomiting and upper respiratory infection. But GW said that over all, the drug was well tolerated.

One caution is that the full details of the study were not released; the company said they would be presented at a medical conference.

GW, which is based in London, said Monday that it would meet with the Food and Drug Administration to see if Epidiolex could be approved based on this single study. It is expecting the results of another trial for Dravet syndrome later this year, and the results of two trials in another form of epilepsy, Lennox-Gastaut.

There are no drugs approved specifically for Dravet syndrome, which typically starts in infancy and affects about 5,000 children in the United States, according to the company. It is not yet known if Epidiolex can help with the walking problems and intellectual disability that can come with Dravet, Dr. Devinsky said.

American depositary receipts of GW closed up about 120 percent on Monday. The company, which specializes in cannabis-based pharmaceuticals, already sells Sativex to treat spasticity associated with multiple sclerosis. It is approved in many countries, though not the United States.

While Epidiolex could be the first prescription drug in the United States extracted from marijuana, two drugs already on the market, dronabinol and nabilone, are synthetic chemicals either similar to or identical to delta-9 THC, the component of marijuana that produces the highs.

Those drugs are approved to treat nausea and vomiting caused by cancer chemotherapy. Dronabinol is also approved to treat weight and appetite loss in patients with AIDS.

GW executives say that an approved pharmaceutical should be favored by doctors and patients because the other medical marijuana products have not gone through the same rigorous vetting.

A study last year by researchers at Johns Hopkins University and elsewhere found that medical marijuana products rarely contained the amount of ingredients stated in their labels.

The F.D.A. has been sending warning letters to some companies, many of them selling hemp oil, saying that they are illegally marketing their products as drugs and that cannabidiol cannot be sold as a dietary supplement because it is being studied for use as a drug.

But even if Epidiolex wins approval, some parents might stick with other products, either because they do not want to disrupt their child’s treatment or they prefer a fuller plant extract to the single ingredient in Epidiolex.

“My kid’s stable. I’m not touching it,” said Allison Ray Benavides, whose 6-year-old son, Robby, is using Charlotte’s Web, to which a little of the psychoactive component THC is added.

Robby used to have 15 to 25 seizures a day, even while taking the approved drug Depakote, and had to wear a helmet all day to protect his head from falls, said Ms. Ray Benavides, a medical social worker in San Diego.

Since starting on Charlotte’s Web more two years ago, while continuing with Depakote, he has had a total of only five seizures.

“I don’t need a double-blind placebo-controlled study to know something,” she said, while nonetheless welcoming the Epidiolex trial results.

Analysts expect Epidiolex to cost $2,500 to $5,000 a month, which would be more expensive than some of the medical marijuana products, which cost from about $100 to more than $1,000 per month. However, Epidiolex might be covered by insurance, unlike the other products.