The development of pharmaceuticals derived from cannabis took a major step forward in June when the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) approved the prescription use of Sativex to treat spasticity due to multiple sclerosis (MS). It is the first time a prescription drug made from cannabis has been approved for sale anywhere in the world.
Developed by GW Pharmaceuticals PLC (London) and marketed in the United Kingdom by Bayer Schering Pharma, Sativex is an oromucosal spray containing mainly tetrahydrocannabinol (THC) and cannabidiol (CBD), two active cannabinoid components isolated from whole plant extracts. Each spray delivers a fixed dose of 2.7 mg THC and 2.5 mg of CBD, which have been shown in clinical trials to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms of MS without creating cannabis intoxication.
“We have been aware for a long time, based on comments from people with MS, that cannabis-based medicines can significantly improve spasticity, which is a common, complex symptom of MS,” said Pam Macfarlane, chief executive of the MS Trust, a UK-based nonprofit that supports research and campaigns for specialist multiple sclerosis services. She called the licensing of Sativex a “milestone.”
The drug, which has been in development for 11 years, works for about half the patients who use it in conjunction with other medications to relieve MS symptoms, Bayer said. The company estimates that roughly 11,500 MS sufferers in the United Kingdom will be eligible to receive Sativex through the government-run National Health Service. Of these individuals, half are likely to get a good response from the treatment.
Bayer gave GW Pharmaceuticals a $15-million milestone payment following MHRA’s licensing approval in June. GW Pharmaceuticals expects regulators in Spain will approve Sativex for MS spasticity by the end of the year, and has licensed the drug’s marketing to Almirall SA in that country as well as in Germany, Italy, and France, where the companies plan to seek marketing approval later this year.
An uphill climb
The commercialization of cannabis-derived pharmaceuticals has been stymied, in part, due to the social and legal stigmas associated with marijuana. But the ongoing debate over medical marijuana may be changing those perceptions. Currently, 15 US states, Canada, the Netherlands, Israel, and several other countries permit doctors to prescribe cannabis to relieve cancer pain and nausea from chemotherapy, improve appetite in AIDS patients, reduce eye pressure from glaucoma, and to treat a range of other serious medical conditions.
The medical marijuana movement in the United States has been bolstered by statements of support from the Obama administration, which last year recommended that federal law enforcement authorities not prosecute patients in states that permit medical usage. Also last year, the American Medical Association reversed its long-standing position that marijuana be retained as a dangerous Schedule I substance having no medical value, and instead affirmed its therapeutic value and called for more research.
As the debate continues, many analysts and scientists foresee an era of respectability, acceptance, and even moderate sales potential for cannabis-related drugs. Analysts at the London-based Piper Jaffray brokerage firm, which advises GW Pharmaceuticals, predict that peak sales in Sativex for MS spasticity could reach $185 million in Europe and Canada.
In the United States, the FDA has given GW Pharmaceuticals permission to enter directly into late-stage clinical trials of Sativex for cancer, and the company reported Phase 2b results in March. GW and marketing partner Otsuka Pharmaceutical Co. of Japan were scheduled to meet with FDA officials this summer to discuss Phase 3 trials. Should Sativex win FDA approval to treat cancer pain in the United States—an option that is several years distant at best—the market could reach $500 million or more annually.
THC is the main psychoactive molecule of cannabis, which confers both its immense recreational status as well as its main pharmaceutical drawback, since patients in clinical settings generally prefer the drug’s analgesic and anti-inflammatory properties without its well-known “high.” Pharmacologic and clinical studies suggest that the CBD component of cannabis also fights inflammation but is non-psychoactive and may even modulate many of THC’s unwanted effects.
Pharmacologists at Lancaster University’s School of Health and Medicine in England are studying the effect of CBD on a range of conditions, including Crohn’s disease, ulcerative colitis, and colorectal cancer. Karen Wright, PhD and her colleagues have found that CBD inhibits intestinal inflammation and reverses microscopic leakage that allows bacteria to spread outside the gut.
Researchers at the Medical College of Georgia at Augusta have demonstrated that CBD can prevent eye damage from diabetes by slowing the action of immune cells that cause inflammation. Gregory Liou, PhD and his colleagues have shown that CBD reduces neurotoxicity, inflammation, and blood-retinal barrier breakdown in diabetic rats.
In addition to THC’s well-known properties of increasing appetite and decreasing nausea for cancer and AIDS patients, reducing eye pressure in glaucoma, and alleviating neuropathic pain and spasticity in certain MS patients, the compound has shown promise in treating post-traumatic stress disorder, Tourette syndrome, ADHD, clinical depression, epilepsy, bipolar disorder, and schizophrenia.
Even more significant perhaps, THC has been shown to selectively trigger programmed cell death in human and mouse cancer and tumor cells while bypassing normal, healthy cells.
Researchers at Complutense University in Madrid reported last year that THC binds protein receptors on cancer cell surfaces, inducing creation and accumulation of ceramide, which activates autophagy and apoptosis. Guillermo Velasco, PhD and his colleagues are seeking to determine whether the effect can be replicated in vivo.
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 13, No. 6, July/August, 2010, p. 6-7.
Filed Under: Drug Discovery