The Medicinal Uses of Cannabis and Cannabinoids. Geoffrey W. Guy, Brian A. Whittle, and Philip J. Robson, eds. Chicago, IL: Pharmaceutical Press; 2004. 488 pp, hardcover. ISBN 0853695172. $65.00.
Every now and then there comes a good book at the right time. The Medicinal Uses of Cannabis and Cannabinoids, edited by Drs. Guy, Whittle, and Robson is such a book, and now is such a time. This book presents evidence of past, present, and even future medical utilizations of both cannabis (i.e., medical marijuana, Cannabis sativa L., Cannabaceae) and the herb’s primary active constituents, the cannabinoids. This information is timely because the matter of medicinal cannabis has entered the modern pharmacopeia. Although a gel capsule of synthetic THC in sesame seed oil has been available for quite some time as dronabinol (Marinol®, Solvay Pharmaceuticals, Inc., Marietta, GA, USA), there are considerable limitations with the oral administration of cannabinoids. And of course, the medicinal use of cannabinoids in both Europe and North America runs parallel to decades of clandestine production, distribution, and oppression of both cannabis and cannabis users in these countries. Also, there seems to be no clear distinction between the medicinal and recreational uses of cannabis. In other words, the desired “side effect” of psychoactivity may be inextricably linked to therapeutic effects.
The wealth of scientific information in this volume will be an important resource for years to come, especially as new derivatives and formulations are introduced. This thoroughly referenced academic text is well written and well organized, and covers the history, botany, phytochemistry, human pharmacology, metabolism, and pharmacokinetics of both exogenous and endogenous cannabinoids in 14 chapters (including an index and glossary). There is also a good amount of information on various cannabis derivatives, including whole plant extracts. To complete the medical perspective, results are presented from recent clinical trials on Sativex®, an oral spray developed by GW Pharmaceutical in the UK from a whole plant extract, for treating chronic pain, symptoms of multiple sclerosis, emesis in chemotherapy, and appetite stimulation in patients with AIDS. Imminently useful information is also presented in other chapters on the subject of cannabis and driving a motor vehicle, along with international perspectives on law and public policy.
On the surface, it seems as if legislators may have been able to see some significant difference between the synthetic THC (i.e., Marinol) and plant-derived THC (e.g., marijuana and its derivatives). But of course, the issue here has been one of control and not medical utility. This is where Sativex begins to enter the historical time line of medicinal cannabis. Moreover, the recent success of Sativex in clinical trials has clearly demonstrated that the medical utility of cannabis is not limited to THC, a fact that has been known to those involved in the medicinal use of marijuana over the last 30-plus years, in addition to historic medical documents that go back over several thousand years. So, again it seems, there is nothing new than what has been forgotten.
Some inevitable overlap exists between a few of these chapters, but these are complex issues that are presented by 16 authors, and many of these topics are worth saying two and even three times. It is also no great secret that the editors do have a financial interest in both editing and contributing to this effort. Thus, one could argue a potential bias, as many of the other authors are also intimately involved in the continuing development and eventual distribution of cannabis medicines for profit. On the other hand, all authors are well informed and in exactly the right positions to know their subject matter. In any event, this volume is a refreshing step away from past decades of emotion-based rationales that have shaped both political opinion and public policy.
In particular, this book is about the difference between the development and delivery of a pharmaceutical product (i.e., doing it) and pre-clinical applications (i.e., still just talking about it). This roughly corresponds to the difference between actually knowing and just guessing about the potential implications of cannabis-based medicines, both medically and economically. The economic aspect is also expected to include the savings achieved by simply removing patients from more toxic medications and on to safer and more efficacious cannabis-based medicines for some indications, in addition to the fact that such plant derivatives are simply less costly to produce than synthetic analogues. As incredible as it seems, this vision is not on some distant academic horizon. Quite recently, Sativex was approved in Canada for treating neuropathic pain in patients with multiple sclerosis. In the EU, however, the availability of Sativex has been put on hold until additional clinical trials have been completed, much to the consternation of GW Pharmaceuticals, various patient groups, and compassionate medical doctors.
Although Marinol remains available, this oral formulation has intractable limitations, which have been recognized over the years, and its monopolized market share can only exist because the legal availability of more efficacious forms of cannabinoid delivery continue to be delayed or proscribed by law. And, after all, Marinol is only THC (and does not include any of the other interesting “impurities” of a whole plant extract). Specifically, the desired effects of THC begin to develop quite slowly after oral delivery. Moreover, a potent psychoactive metabolite is formed by the liver, which makes the patient “higher” than if he/she had simply taken the spray, sucked on a lozenge, or smoked a joint. A THC suppository is also available, and even though this route of administration is relatively fast and does bypass the liver, who really wants this inconvenient method of drug delivery when a spray, or a puff, will do?
No! Enough already! We have finally arrived at a new plateau for medicinal cannabis, in a world of sophisticated medical delivery systems for the safe and rapid administration of standardized cannabinoids in dose-controlled, patient-titratable sprays of liquid bliss. This is the obvious quantum leap forward from inhaling the vapors of burned flowers, at best, and popping hot seeds on the patients’ bedspread with gratuitous pieces of “lumber” at worst. Finally, we can enjoy the benefits of modern technology to deliver cannabinoids in the same ways already enjoyed by so many other medicaments, most of which have only recently been introduced to our species. Imagine how effective wide-spread cannabis use might be with the sudden introduction of such a device or formulation; as if both the actual political risks and potential health concerns from smoked marijuana suddenly and simultaneously dissipated into a waft of thin air, leaving just the patient and the medicine to work it out under the gentle supervision of an informed physician. But are we really there yet? Well, yes and no.
Smoking marijuana is still the most efficient and effective way to administer the natural components of cannabis, and millions of people will continue to use this form of delivery for a long time to come and for a wide variety of reasons. However, the inhalation of any burnt offering may not ever be more widely acceptable to modern medicine than it is now, and most medical patients should probably not be smoking something anyway. Eating cannabis can also be effective, but quality control and dose titration are obvious and complex drawbacks, as with Marinol. Thus, a standardized plant extract, delivered by a septic inhalation device, a lozenge, or a spray under the tongue, will be the obvious ways forward in the modern world of acceptable pharmaceuticals.
The lingering issues around cannabis prohibition are also complex, and the overall result of this dubious effort has been an incredibly huge and effective propaganda machine over the last 70-plus years, where political truths and opinions have become deeply entrenched as hard wired “facts.” These topics are also discussed in this book. Realistically, most of the recent change concerning the politics of cannabis has basically come through political attrition during the last decade; i.e., the ideological resistance is simply retiring and dying at a sure and steady rate, in addition to recent realizations that there may be more important things for law enforcement and military resources to do than bully peaceful pot smokers and/or medical marijuana patients. Another important component of change has also come from the efforts of politics, albeit more indirectly; i.e., through the public funding of various scientific efforts to establish the putative toxicity of cannabis and cannabinoids over the last 40-plus years. Of course, these efforts have only revealed new medicines (such as Marinol/THC) and have firmly established that, in fact, the natural cannabinoids are surprisingly lacking in either acute or chronic toxicity, even under the most determined experimental designs. And, unlike the motivations of earlier toxicological investigations, the recent discovery of an endogenous cannabinoid system has come out of pure scientific interest and not through a stated political agenda. This is the stage where the matters of medical cannabis have developed over the years, where time and cool logic have been the producer and director, respectively. The audience has been patient. More tragedy than comedy, it is ironic to realize that all this hysteria has been about THC, the sole component of Marinol, or so it seems. And yet we still need more scientific evidence to show what? Again, the authors help us put these matters into perspective.
This book also describes the tedious process that has led to the successful registration of Sativex. These efforts coincide with the simultaneous unfolding of basic medical research into phyto-cannabinoids, endo-cannabinoids, and the discovery of a complex endogenous network of ligands and cannabinoid receptors within us all. The wide range of potential medical indications for cannabis and cannabinoids, and the potential economic savings to both private and governmental health systems are striking. Again, the overused term “panacea” comes to mind.
On a more practical level, this book also includes important chapters on the genetic pedigree of existing cannabis varieties, and it demonstrates the pharmacologic importance of cannabinoid profiles; i.e., some lines producing just THC while some others reliably produce various combinations of THC and other useful cannabinoids, along with the usual terpenes and other minor components of a whole plant extract. Established lines of genetically set cannabinoid profiles, reproduced as cloned fields of green under a matrix of high pressure sodium lamps, standardized extraction methods, and a final delivery device are exactly the features required of a modern medicament to fit seamlessly into the pharmacy without all the emotional baggage and pyrolysis of “marijuana.” Such an approach is yet another positive force that runs counter to 70-plus years of fear, ignorance, and faith-based testimony on matters of cannabis, and it runs parallel to the well-established medical marijuana movements in those countries where cannabiphobia has reached epidemic proportions.
Digressing just a bit from this heady collection of radical science, ignorant politics, and medical fact, one must occasionally wonder why a plant would even want to produce a cannabinoid, as cannabis is the only living species known to do so. As a form of protection, perhaps, against ionizing UV-B radiation from the sun, or simply a highly specified gooey resin that makes it difficult for insects to chew? And why do humans and so many other eukaryotic organisms have discreet receptors for botanical cannabinoids, let alone our own systems for producing the endo-cannabinoids from linoleic acid, a common omega-6 dietary fatty acid? And, could it be any coincidence at all that the seed oil of cannabis typically contains over 50% linoleic acid, the essential precursor to our endo-cannabinoids, as well as the entire arachidonic acid cascade? The mind begins to reel at the evolutionary implications, and there is discussion in this book of these matters as well.
This authoritative, well-referenced book is recommended to anyone who has even a passing interest in the medical significance of cannabis, and it is a valuable resource to either the student, scientist, or physician who has any desire to learn more about this fascinating topic. It may even help alleviate the symptoms of cannabiphobia in some. Without a doubt, this literary effort by Guy et al has accomplished its purpose. The only thing lacking, in my opinion, was a complimentary sample of Sativex. Rapid progress will continue in the field of medicinal cannabis, particularly as the remaining obstacle of regressive politics continues to melt away with time, and especially as more legislators begin to fill the void with matters more important than trying to control the personal use of flowers.
—J.C. Callaway, PhD, Adjunct Professor of Ethnopharmacology, Dept. of Pharmaceutical Chemistry, University of Kuopio, Finland.