Posts Tagged ‘Cannabinoid’
A compound found in marijuana can treat schizophrenia as effectively as antipsychotic medications, with far fewer side effects, according to a preliminary clinical trial.
Researchers led by Markus Leweke of the University of Cologne in Germany studied 39 people with schizophrenia who were hospitalized for a psychotic episode. Nineteen patients were treated with amisulpride, an antipsychotic medication that is not approved in the U.S., but is comparable to other medications that are.
The rest of the patients were given cannabidiol (CBD), a substance found in marijuana that is thought to be responsible for some of its mellowing or anxiety-reducing effects. Unlike the main ingredient in marijuana, THC, which can produce psychotic reactions and may worsen schizophrenia, CBD has antipsychotic effects, according to previous research in both animals and humans.
Neither the patients nor the scientists knew who was getting which drug. At the end of the four-week trial, both groups showed significant clinical improvement in their schizophrenic symptoms, and there was no difference between those getting CBD or amisulpride.
“The results were amazing,” says Daniel Piomelli, professor of pharmacology at the University of California-Irvine and a co-author of the study. “Not only was [CBD] as effective as standard antipsychotics, but it was also essentially free of the typical side effects seen with antipsychotic drugs.”
Antipsychotic medications can potentially cause devastating and sometimes permanent movement disorders; they can also reduce users’ motivation and pleasure. The new generation of antipsychotic drugs also often leads to weight gain and can increase diabetes risk. These side effects have long been known to be a major obstacle to treatment.
In the German study, published online in March by the journal Translational Psychiatry, weight gain and movement problems were seen in patients taking amisulpride, but not CBD.
“These exciting findings should stimulate a great deal of research,” says Dr. John Krystal, chair of psychiatry at Yale University School of Medicine, who was not associated with the research. He notes that CBD not only had fewer side effects, but also seemed to work better on schizophrenia’s so-called “negative symptoms,” which are notoriously hard to treat.
Negative symptoms include social withdrawal, blunting of pleasure and lack of motivation, which commonly occur in schizophrenia. Since current antipsychotic medications can themselves cause the same problems, however, it wasn’t clear whether CBD was better than amisulpride at treating these symptoms, or whether CBD simply caused fewer side effects to begin with.
Nevertheless, the new research helps elucidate the intricate complexities of the brain’s natural cannabinoid system and how CBD may work to alleviate symptoms of schizophrenia. Years ago, Piomelli and his colleagues discovered that people with schizophrenia have elevated levels of anandamide — a neurotransmitter that activates the same receptor activated by THC — in their cerebrospinal fluid, suggesting that they also had higher levels of it in the brain.
The difference was huge: anandamide levels were nine times higher in schizophrenic people than in mentally healthy controls, Piomelli says.
The researchers theorized that these radically high levels would correlate with hallucinations and delusions: the more anandamide bathing patients’ brains, the worse their disease would be. The thinking was, in essence, that people with schizophrenia are constantly high on their own natural THC.
But what the researchers actually found was the opposite. “What you get is not a positive correlation, but a negative one. The higher the levels of anandamide, the lower the symptoms,” Piomelli says.
It didn’t seem to make much sense at first, but research in both animals and humans now shows that anandamide is a natural stress reliever and antipsychotic. Piomelli thinks that the high levels seen in people with schizophrenia aren’t the cause of the problem, but the result of the brain’s attempts to solve it.
The new study confirmed that as CBD relieved patients’ symptoms, anandamide levels rose in concert. “It looks like anandamide is a signaling molecule that has evolved to help us cope with stress,” Piomelli says. “In the brain, everything it does seems to be related to ways of relieving stress. It can relieve anxiety and reduce the stress response. It is involved in stress-induced analgesia [when you stop feeling pain while fighting or fleeing]. These are all mechanisms to help us prevent [negative outcomes related to stress],” says Piomelli.
“If Dr. Piomelli is right, then the brain is exquisitely sensitive to changes in anandamide levels,” says Krystal.
This raises another question, however. THC itself mimics anandamide. If high levels of anandamide are helpful for schizophrenia, why does marijuana smoking intensify psychotic states?
Here’s where it gets complex. THC mimics not only anandamide, but also another cannabinoid, 2-AG, which fits the same receptors and is far more common. “There is 200 times more 2-AG than anandamide in the brain,” Piomelli says. “At the end of the day, the complexity is such that 2-AG has a whole cluster of effects. Anandamide has completely different effects, sometimes even opposite effects. That is why with THC you get a big mess.”
Complicating matters further, when chronic marijuana smokers build up a tolerance to THC, it may down-regulate the entire system, making it harder for anandamide to have its positive effects. This may be why some studies find that people with schizophrenia who smoke marijuana get worse.
So, where does CBD fit in? It doesn’t attach to a receptor like THC, or fool the brain into thinking that it’s getting extra anandamide or 2-AG. “What CBD seems to be doing is preventing anandamide from being destroyed,” says Piomelli. That allows the substance to exert its stress-reducing and antipsychotic effects on the brain longer, without the negative effects of THC.
If replicated, the results suggest that CBD may be at least as effective as existing drugs for the treatment of schizophrenia, without the severe side effects that make patients reluctant to take medication. The catch: “The real problem with CBD is that it’s hard to develop for a variety of silly reasons,” says Piomelli.
Because it comes from marijuana, there are obvious political issues surrounding its use. Extracting it from the plant is also expensive. But the biggest barrier may be that CBD is a natural compound, and therefore can’t be patented the way new drugs are. That means that despite the possibility that it could outsell their current blockbuster antipsychotic drugs, pharmaceutical companies aren’t likely to develop it — a particularly striking fact when you consider that every major manufacturer of new generation antipsychotics in the U.S. has so far paid out hundreds of millions or billions of dollars in fines for mismarketing these drugs. Yet they still reaped huge profits.
Piomelli and others are working to develop synthetic versions of CBD that would avoid such hurdles. “We have one and are hoping to move forward in the near future,” he says.
For people with schizophrenia and their families, of course, it is likely to be infuriating that non-scientific issues like marijuana policy and patenting problems could stand in the way of a treatment that could potentially be so restorative. While it’s possible that these study results may not hold up or that researchers could discover problems related to long-term use of CBD, it’s hard to imagine that they could be any worse than what patients already experience.
By Raymond Cushing, AlterNet
The term medical marijuana took on dramatic new meaning in February, 2000 when researchers in Madrid announced they had destroyed incurable brain tumors in rats by injecting them with THC, the active ingredient in cannabis.
The Madrid study marks only the second time that THC has been administered to tumor-bearing animals; the first was a Virginia investigation 26 years ago. In both studies, the THC shrank or destroyed tumors in a majority of the test subjects.
Most Americans don’t know anything about the Madrid discovery. Virtually no major U.S. newspapers carried the story, which ran only once on the AP and UPI news wires, on Feb. 29, 2000.
The ominous part is that this isn’t the first time scientists have discovered that THC shrinks tumors. In 1974 researchers at the Medical College of Virginia, who had been funded by the National Institute of Health to find evidence that marijuana damages the immune system, found instead that THC slowed the growth of three kinds of cancer in mice – lung and breast cancer, and a virus-induced leukemia.
The DEA quickly shut down the Virginia study and all further cannabis/tumor research, according to Jack Herer, who reports on the events in his book, “The Emperor Wears No Clothes.” In 1976 President Gerald Ford put an end to all public cannabis research and granted exclusive research rights to major pharmaceutical companies, who set out – unsuccessfully – to develop synthetic forms of THC that would deliver all the medical benefits without the “high.”
The Madrid researchers reported in the March issue of “Nature Medicine” that they injected the brains of 45 rats with cancer cells, producing tumors whose presence they confirmed through magnetic resonance imaging (MRI). On the 12th day they injected 15 of the rats with THC and 15 with Win-55,212-2 a synthetic compound similar to THC. “All the rats left untreated uniformly died 12-18 days after glioma (brain cancer) cell inoculation … Cannabinoid (THC)-treated rats survived significantly longer than control rats. THC administration was ineffective in three rats, which died by days 16-18. Nine of the THC-treated rats surpassed the time of death of untreated rats, and survived up to 19-35 days. Moreover, the tumor was completely eradicated in three of the treated rats.” The rats treated with Win-55,212-2 showed similar results.
The Spanish researchers, led by Dr. Manuel Guzman of Complutense University, also irrigated healthy rats’ brains with large doses of THC for seven days, to test for harmful biochemical or neurological effects. They found none.
“Careful MRI analysis of all those tumor-free rats showed no sign of damage related to necrosis, edema, infection or trauma … We also examined other potential side effects of cannabinoid administration. In both tumor-free and tumor-bearing rats, cannabinoid administration induced no substantial change in behavioral parameters such as motor coordination or physical activity. Food and water intake as well as body weight gain were unaffected during and after cannabinoid delivery. Likewise, the general hematological profiles of cannabinoid-treated rats were normal. Thus, neither biochemical parameters nor markers of tissue damage changed substantially during the 7-day delivery period or for at least 2 months after cannabinoid treatment ended.”
Guzman’s investigation is the only time since the 1974 Virginia study that THC has been administered to live tumor-bearing animals. (The Spanish researchers cite a 1998 study in which cannabinoids inhibited breast cancer cell proliferation, but that was a “petri dish” experiment that didn’t involve live subjects.)
In an email interview for this story, the Madrid researcher said he had heard of the Virginia study, but had never been able to locate literature on it. Hence, the Nature Medicine article characterizes the new study as the first on tumor-laden animals and doesn’t cite the 1974 Virginia investigation.
“I am aware of the existence of that research. In fact I have attempted many times to obtain the journal article on the original investigation by these people, but it has proven impossible.” Guzman said.
In 1983 the Reagan/Bush Administration tried to persuade American universities and researchers to destroy all 1966-76 cannabis research work, including compendiums in libraries, reports Jack Herer, who states, “We know that large amounts of information have since disappeared.”
Guzman provided the title of the work – “Antineoplastic activity of cannabinoids,” an article in a 1975 Journal of the National Cancer Institute – and this writer obtained a copy at the University of California medical school library in Davis and faxed it to Madrid.
The summary of the Virginia study begins, “Lewis lung adenocarcinoma growth was retarded by the oral administration of tetrahydrocannabinol (THC) and cannabinol (CBN)” – two types of cannabinoids, a family of active components in marijuana. “Mice treated for 20 consecutive days with THC and CBN had reduced primary tumor size.”
The 1975 journal article doesn’t mention breast cancer tumors, which featured in the only newspaper story ever to appear about the 1974 study – in the Local section of the Washington Post on August 18, 1974. Under the headline, “Cancer Curb Is Studied,” it read in part:
“The active chemical agent in marijuana curbs the growth of three kinds of cancer in mice and may also suppress the immunity reaction that causes rejection of organ transplants, a Medical College of Virginia team has discovered.” The researchers “found that THC slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent.”
Guzman, writing from Madrid, was eloquent in his response after this writer faxed him the clipping from the Washington Post of a quarter century ago. In translation, he wrote:
“It is extremely interesting to me, the hope that the project seemed to awaken at that moment, and the sad evolution of events during the years following the discovery, until now we once again Îdraw back the veilâ over the anti-tumoral power of THC, twenty-five years later. Unfortunately, the world bumps along between such moments of hope and long periods of intellectual castration.”
News coverage of the Madrid discovery has been virtually nonexistent in this country. The news broke quietly on Feb. 29, 2000 with a story that ran once on the UPI wire about the Nature Medicine article. This writer stumbled on it through a link that appeared briefly on the Drudge Report web page. The New York Times, Washington Post and Los Angeles Times all ignored the story, even though its newsworthiness is indisputable: a benign substance occurring in nature destroys deadly brain tumors.
Raymond Cushing is a journalist, musician and filmmaker. This article was named by Project Censored as a “Top Censored Story of 2000.”