Cannabinoids as Therapeutics

Imagine that you have spent more than four decades studying an ancient Indian herbal medicine. After you have isolated and solved the chemical structure of the major active principle of this herbal medicine, you and international colleagues show that this herb has clinical efficacy in treating the nausea of cancer chemotherapy, the pain of multiple sclerosis and other causes of neuropathic pain, anxiety, gastrointestinal spasms, and the loss of appetite associated with HIV and cancer. In the USA, such a herbal medicine would most surely have received an accelerated botanical Investigational New Drugs and be pushed through clinical trials to confirm its decades- and centuries-old clinical utility. As a pharmacologist, I’d argue that the herb would be so widely beneficial that the discoverer of its active constituents and promoter of its biological study should stand to receive a Nobel Prize in Medicine or Physiology.

Instead, Raphael Mechoulam of the Hebrew University in Jerusalem must be content to have overseen the most scholarly, complete and readable volume in the Milestones of Drug Therapy series. Mechoulam and coauthors of chapters in this outstanding book have devoted their chemistry and pharmacology careers to the study of a natural, plant-based medicine whose only fault is its enthusiastic use by 1960s counterculture Vietnam War protesters and 1930s jazz musicians. Unlike wine and beer, whose ethyl alcohol made France a cultural centre and fuelled the US colonial rebellion from its mother land, marijuana (or cannabis) has been the unjust victim of misunderstanding and misrepresentation.

The book is worth the price of admission even for the opening and closing chapters by representatives from GW Pharmaceuticals alone, whose buccal mucosal cannabis spray is about to become the first worldwide cannabis-based herbal medicine given prescription drug approval for the management of pain and nausea. Ethan Russo opens with an exhaustive chapter on cannabis in India: ancient folklore and modern medicine while his colleague, Geoffrey Guy, closes with the development of Sativex. While the intended audience is clearly the neuroscience research community, so much of the book appeals to the recreational cannabis enthusiast, botanist, herbalist and student of Ayurvedic medicine.

The authority of the book comes, of course, from Mechoulam, whose second chapter on cannabinoid chemistry modestly describes the seminal contributions of his group over many years. International cannabis prohibitionists have nowhere to hide when reading the chapters on the isolation and activity of endogenous cannabinoids such as anandamide, so-named after the ancient text Anandakanda, whose 43 Sanskrit synonyms for cannabis speak of its rejuvenating biological effects. Reading the book reminded this pharmacologist that the second endogenous cannabinoid receptor, the non-psychoactive CB2 subtype, was identified originally on HL-60 human leukaemia cells. No surprise then that cannabinoids have been shown to exhibit antitumour activities.

In general, the book meets the needs of any scholar of cannabis research. While heavy on the neuropharmacology of the active constituents, the book is rich in the history, botany, chemistry and drug development of this medicinal plant. The unique story of the cultivation of two cannabis cultivars to produce THC and the non-psychoactive cannabidiol in the form of a buccal spray pharmaceutical formulation defines not only the proper way to develop a herbal medicine for therapeutic use, but also demonstrates the tenacity of cannabis researchers to overcome the collision of politics and science in the name of benefit for patients in need of pain management with nearly no addiction liability.

Some may argue that approval of a regulated pharmaceutical preparation of cannabis is just as offensive as outlawing the personal propagation of Cannabis sativa for personal use. However, during the review of this book, the Bush administration-fuelled US Food and Drug Administration declared medicinal marijuana to be of no therapeutic use despite a US National Academy of Sciences/Institute of Medicine review much to the contrary several years earlier. Unfortunately, it will take the pharmaceutical development of this herbal medicine in the paradigm of modern drug development to realise the promise suggested by central Asian writings over 2000 years old.

David Kroll reports a potential conflict of interest in that chemists in his research unit provide contract syntheses of cannabinoids for research purposes.