Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

New crop of companies are adding to the political debate and also providing clinical evidence.

In one of the only U.S. clinical trials testing the medicinal properties of inhaled Cannabis sativa, results confirmed that pot was effective in reducing muscle spasms associated with multiple sclerosis and pain caused by certain neurological injuries or illnesses. The trial, sponsored by the California-funded Center for Medical Cannabis Research at the University of California, San Diego, enrolled participants suffering from multiple sclerosis, AIDS, or diabetes along with healthy volunteers injected with a chili pepper substance to induce pain. They were randomly assigned to receive cigarettes filled with marijuana.

The results were comparable to the percentage of people who experience relief after taking other pain medications. “This is the first step in approaching the [FDA], which has invested absolutely nothing in providing scientific data to resolve the debate,” said state Senator Mark Leno (D. San Francisco).

The U.S. Government spent heavily on the first approved cannabis-based drug, Marinol®, back in 1985. The drug was developed by Unimed, now a subsidiary of Solvay Pharmaceuticals. FDA also approved Valeant Pharmaceuticals’ Cesamet the same year. Both drugs, however, are synthetic versions of one active marijuana constituent, delta-9-tetrahydrocannabinol (ΔTHC.)

The FDA sanctioned Marinol to treat nausea and vomiting associated with chemotherapy in patients who do not respond adequately to conventional medications as well as appetite loss associated with weight loss in AIDS patients. Cesamet, developed as an antiemetic and an adjunct analgesic for neuropathic pain, was not marketed in the U.S. until 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS.

The distinction between inhaled Cannabis sativa and an approved pharmaceutical hinged, at the time of the drugs’ approval, on separating the psychoactive properties of some of marijuana’s constituents and the medicinal properties of others. A 1999 report commissioned by the The White House Office of National Drug Control stated that “marijuana is not a completely benign substance. It is a powerful drug with a variety of effects.

“However, the harmful effects to individuals from the perspective of possible medical use of marijuana are not necessarily the same as the harmful physical effects of drug abuse. Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke. In addition, plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect.”

The report went on to conclude that “the future of cannabinoid drugs lies not in smoked marijuana but in chemically defined drugs that act on the cannabinoid systems that are a natural component of human physiology.” The White House commissioned the 267-page report shortly after voters in California passed the Compassionate Use Act of 1996, which legalized the medical use of cannabis under state law.

And on March 18 of this year, GW Pharmaceuticals said that Sativex, its oral mucosal cannabinoid spray, should be approved in the U.K. and Spain soon. Both countries concluded that there are no major quality, safety, or efficacy issues remaining to be resolved. Details about final wording on the patient information leaflet is reportedly all that is left to be ironed out.

A few days later, the company announced Phase IIb results of Sativex in patients with advanced cancer who experience inadequate analgesia during optimized chronic opioid therapy. The trial recruited a total of 360 patients in 14 countries in North America, Europe, Latin America, and South Africa and evaluated three dose ranges. Sativex produced statistically significant differences from placebo in pain scores, supporting advancement into Phase III, according to the company.





Beyond Pharmaceuticalization

The emergence of public companies pursuing the development of legalized cannabis products may provide a new crop of useful drugs. On March 24, 2009, Medical Marijuana became the first public corporation solely based on medical marijuana. Bruce Perlowin, the company’s CEO, established the firm as a step toward legitimizing the industry after decades of advocating the benefits of legalizing medical marijuana.

Richard Cowan, Cannabis Science’s CFO, noted that the segment got another boost on May 24 of this year when 15 members of Congress led by U.S. Representative Barney Frank (D. MA) urged the Treasury Department to set rules that encourage banks to provide financial services to medical marijuana clinics, which they consider lawful businesses. “This is just one more important step toward a realistic federal policy on medical marijuana,” Cowan noted.

A policy that would assure banks that they won’t be targeted for doing business with companies that distribute medical marijuana, would definitely benefit Cannabis Sciences as it buys up experienced growers. On May 24, the company acquired RockBrook, a fully licensed dispensary providing patients in Colorado with medical marijuana as well an experienced grower of medical cannabis in accordance with state laws.

Cannabis Science used to be Gulf Onshore and changed its name after acquiring Cannex Therapeutics. The company is developing products both with and without psychoactive properties to treat disease and the symptoms of disease as well as for general health maintenance. It is looking to partner IND filing and clinical development.

Cannabis Science plans to develop a whole cannabis extract lozenge as its first pharmaceutical product. Initial findings from informal human trials using the whole-cannabis extract demonstrated that it has the capacity to enhance rapid onset pain relief through oral mucosal absorption. The lozenge is a part of the assets and know-how acquired through Cannex.

On June 1, the company said that it was working toward picking up a private company that owned complementary patented intellectual property for specific clinical-stage cannabinoid products and uses.

“It seems inevitable that at least for some period of time there will co-exist two distribution pathways for this medicine,” noted Lester Grinspoon, M.D., emeritus professor of psychiatry at Harvard and long-time advocate for the legalization of marijuana, “first, the conventional model of modern allopathic medicine through pharmacy-filled prescriptions for FDA-approved medicines, and second, a model closer to the distribution of alternative and herbal medicines, where there is little if any quality or quantity control. Either way, growing numbers of people will become familiar with cannabis and its derivative products.”

As individual U.S. states move toward either legalization of marijuana or approval of its medical use, the new corporate voices are adding to the pro-pot choir. These companies can potentially help advance the political debate by providing the long-needed clinical trials to validate specific medical applications of Cannabis sativa and its constituent compounds.

Separating psychoactive from medicinal properties through “pharmaceuticalization” of marijuana may be unrealistic. According to NIH, Cesamet “has complex effects on the central nervous system. Its effects on the mental state (i.e., “inner mental life”) are similar to those of cannabis. Subjects given Cesamet may experience changes in mood (euphoria, detachment, depression, anxiety, panic, paranoia), decrements in cognitive performance and memory, a decreased ability to control drives and impulses, and alterations in the experience of reality (e.g., distortions in the perception of objects and the sense of time and hallucinations.”

At least 66 other cannabinoids are also present in cannabis, including cannabidiol, cannabinol, and tetrahydrocannabivarin, which are believed to result in different effects than those of THC alone. Apart from significant difficulties associated with titrating appropriate effective doses, inhaling smoke—which can be avoided through marijuana vaporization—and psychoactive effects, the whole weed may remain the real deal.

































































































































































Patricia F. Dimond, Ph.D., is a principal at BioInsight Consulting. Email: drpdimond@genengnews.com.