AAMC: Interview with Dr. Lester Grinspoon in Cannabis Health Journal

Lester Grinspoon MD is an emeritus associate professor of psychiatry at Harvard Medical School. He has been studying cannabis since 1967 and has published two books on the subject: "Marihuana Reconsidered" (Harvard University Press, 1971) and "Marihuana, the Forbidden Medicine", co-authored with James B. Bakalar (Yale University Press, 1993). He maintains two active websites: The Medical Marijuana website (www.Rxmarijuana.com) and The Uses of Marijuana website (www.marijuana-uses.com).

Lester is truly one of the most respected and loved marijuana advocates in the world. His compassion and commitment to the truth keep him, at 77, active in the reform movement and he continues to give his time to all of us in so many ways. On behalf of all the volunteers and supporters of Cannabis Health we would like to thank him, from the bottom of our hearts. It has been our honor to be able to work with him.

Lester Grinspoon: That is a good description of herbal marijuana, which is comprised of all of the therapeutically useful elements, some of which probably behave synergistically, and some have yet to be identified. If the extracts McPartland and Russo speak of contained all of these elements, they would have the potential for being as clinically useful as whole smoked or vaporized cannabis. However, because they are not intended to be taken through the pulmonary system, they are handicapped in any medical competition with herbal marihuana.

CH: GW recently stated in a press release: "Sativex is not liquid marijuana - Sativex is a pharmaceutical product standardized in composition formulation, and dose administered by means of an appropriate alternative delivery system, which has been, and continues to be, tested in properly controlled preclinical and clinical studies. Crude herbal cannabis-often called 'marijuana'- in liquid or any other form is none of those things".

LG: Over the 38 years during which I have been studying cannabis I have been so impressed by both its very limited toxicity and its versatility as a medicine that I should think that GW Pharmaceuticals would not take umbrage with the description of Sativex as "liquid marijuana"; I would see it as a compliment. However, I think these folks have undertaken a bold endeavor to make use of the anecdotal data generated by medical marijuana users to create a pharmaceutical product which now requires them to persuade the world that manipulated orange juice is safer, easier to deal with and healthier than whole oranges; and, of course, it's worth the extra cost. It's an absurd proposition but GW Pharmaceuticals has to persuade would-be medical cannabis users that there is a significant therapeutic difference between Sativex, an extract of marijuana, and herbal marijuana.

I believe that they will not be very successful in selling this extract unless they succeed in making this distinction. However, if the prohibition gets more severe, interest in Sativex is likely to increase in the same way it has for Marinol --not because it is a better and safer medicine than herbal marihuana, but because it is not illegal. If the prohibition were to disappear and Sativex had to compete with herbal marijuana on a level playing field, Sativex would probably suffer a fate similar to that of Marinol; some people would use it, some might even prefer it, but it would not be a major means by which people make use of the therapeutic utilities in marijuana.

If marijuana had been allowed to be researched in the appropriate way for such a widely used medicine, it would long since have been "tested in properly controlled preclinical and clinical studies." It's a little inaccurate for GW to say Sativex marks the world's first approval of a cannabis-derived medicine. Does GW not think that Nabilone or Marinol are cannabis-derived medicines? In the literal sense Sativex comes from a marijuana plant as opposed to a synthetic compound, but those drugs are cannabis-derived medicines as well. Contemporary governments may not approve herbal marijuana as a medicine but a significant fraction of the medical marijuana patients of the world use it as a medicine, have done so for centuries, and will continue to do so.

LG: By the mid-19th century, there were a number of drug companies who were producing Cannabis indica, the generic name at the time for extracts of marijuana. One that was commonly used was Tilden's Extract, the brand that Fitz Hugh Ludlow decided to use. He was emulating writers of the French Romantic literary movement, members of Le Club des Haschischins who would take large amounts of hashish, which together with their effusive imaginations, led to extraordinary and often distorted accounts of cannabis experiences. In fact, in my opinion, these descriptions led to some of the myths which, until recently, surrounded marijuana. These exaggerated accounts even percolated down to Harry Anslinger [architect of US prohibition], although he almost certainly didn't read them directly.

Extracts such as Tilden's were most commonly used to treat insomnia and pain. They could be purchased from the local apothecary up until the Marijuana Tax Act was passed in 1937. Bayer (the same company which is now partnering with GW Pharmaceuticals to distribute Sativex) produced the first synthesized acetylsalicylic acid, or Aspirin, in 1898. Physicians now could prescribe these little white pills that would relieve mild to moderate pain. In 1900 the first of the barbiturates was synthesized, and others came rapidly on its heels. Now there were pills that one could prescribe for sleep. The Marijuana Tax Act was not meant to contribute to the demise of cannabis as a medicine, but the kinds of paperwork created by the Act discouraged physicians from prescribing it. Consequently, with the arrival of these new drugs which successfully treated insomnia and pain, the two symptoms for which Cannabis indica was most commonly prescribed, its use declined. It was removed from the pharmacopoeia in 1941.

LG: Physicians of the 19th century never discovered the remarkable boon of using cannabis with a pulmonary delivery application. Physicians at that time couldn't control the dose with any degree of precision because they didn't even know the potency of the Cannabis indica they were prescribing. However, they weren't too concerned, because if a patient did get too large a dose, there were no serious consequences, although a patient might be uncomfortable for a while. Physicians were more concerned about under-dosing and the fact that it took an hour or so for this medicine to take effect.

LG: It's not as fast as smoking but not as slow as the oral route. You have to wait at least 20 minutes for a sublingual effect. At first GW claimed that Sativex is totally absorbed through the mucosa under the tongue. But the fact is, the extract tastes awful and some people find it very uncomfortable; they can't hold it under the tongue long enough and it drips down into the esophagus. I would suspect that most applications of sublingual Sativex actually end up with an unknown proportion going the sublingual route and the other part of it going orally. There would then be two kinds of titration points, one at 20-40 minutes, the other not until 1-2 hours have passed.

To me the sublingual route is an inefficient way of taking a medicine when it is available in a form that allows for much more precision in titration. Furthermore, the titration precision of the pulmonary route allows the physicians to give the patient the responsibility for establishing his own dosage. After all, it is the patients who can say when they have achieved relief of their symptoms. It's not the doctors, not the pharmacists; it's the patients. We allow patients to take their own over-the-counter medicines. Even though more than 16,000 people die every year in the United States from idiopathic gastric bleeding and other toxic effects caused by Nonsteroidal Anti-Inflammatory Drugs (NSAIDS), we allow them to take ibuprofen, aspirin and other NSAIDS over-the-counter and trust that they will use them responsibly. It simply doesn't make any sense to forbid patients the responsibility to use herbal marihuana and the freedom to titrate their own dose.

LG: This is a no-brainer; of course one can. If it contains THC one can certainly get high and predictably there will be people whose main interest in Sativex will be to achieve the psychoactive effect. Furthermore, some patients will inadvertently experience the psychoactive effects for the first time with Sativex either because the dose can't be titrated as precisely as when it is smoked or the therapeutic dose is too close to, or overlaps with, the psychoactivity dose.

LG: One of the selling points of Sativex is that you don't have to smoke it and run the risk of serious pulmonary damage. There is very little evidence of this. In the 1960s when I began to write about this, some people said, "Of course there's no pulmonary cancer; we in this country haven't been using it very long." But look, here we are in 2005 and people in your country and mine and many other places around the world have been smoking it for decades now. And yet we have not seen cases of lung cancer or emphysema that are due to smoking marijuana alone. I wouldn't be surprised if we eventually find them in Europe where cannabis is frequently mixed with tobacco.

In the anti-smoking environment we live in, many people believe that smoking anything is detrimental to the pulmonary system. I, personally, believe that living in a polluted urban environment represents more of a pulmonary risk. And those who are made uncomfortable by smoking can now use a vaporizer and get the same effects without smoke. There is no smoke. The cannabinoids volatilize off in a temperature window; and when you remove the spent material from the vaporizer you can see it hasn't been turned into ashes because it hasn't been ignited.

LG: Smoking allows for a very fine tuning of the dose. One of the things that makes cannabis such an impressive medicine is the fact that it can be taken through the lungs either directly or through a vaporizer, which gives a patient the capacity to titrate the dose quickly, to get just the amount needed to get relief and no more. To me this is a great benefit, not just from the point of delivering a medicine at the right dose, but also because it gives the patient, the best judge of his needs, control.

LG: The GW people, in order to successfully sell their product, have to persuade people that there is a real danger to smoking marijuana. This plays into the hands of the prohibitionists. The argument goes: we are just getting on top of the tobacco problem, cigarette consumption has gone down. Clearly tobacco consumption is very dangerous, so why should we have another smokeable drug that will lead to the same kind of catastrophic health consequences. The problem with the argument is that there is very little empirical data to support equating the consequences of smoking marijuana to those of smoking tobacco.

LG: From my clinical experience, I am not sure that in any of the many different ways in which cannabis is used as a medicine, that the therapeutic goal can always be successfully achieved completely free of any psychoactive effect. I am also not certain that even if it were possible, that eliminating the psychoactive effects is a good idea. For example, people who suffer from multiple sclerosis who use marijuana primarily to get relief from pain and muscle spasms often say, "It makes me feel better." There are two aspects to that; one is that they are getting symptom-relief and that makes them feel better. But clearly there is something beyond that and I believe it to be a function of the fact that they have some psychoactive, perhaps antidepressant effect.

It's becoming increasingly important in medicine to recognize that people who feel better generally do better. Those who have a better attitude about their disease or disability tend to do better. Assuming there is some dosage difference between the point where cannabis can relieve the symptom and the point where there is some psychoactive effect, wouldn't it better for those who want to avoid the psychoactive effect to be able to titrate it more finely than in the coarse way that Sativex is said to be titrated? You can't really titrate in the usual sense of the word with an oral preparation of marijuana whether it be Marinol, Sativex or herbal marijuana brownies. If you suffer from chronic pain from some kind of serious arthritic condition, such as ankylosing spondylitis, you might want an oral preparation because its effects last longer. But in those situations where you have severe nausea and vomiting, or the painful cramping of Crohn's disease or some kind of neuropathic pain and you want immediate relief, the way to get it is by smoking. If you experience the prodrome of either a migraine attack or a convulsive episode, you may be able to nip it in the bud quickly by smoking.

LG: In many situations patients are the best judges and certainly, once patients understand how to properly use cannabis, it's both safe and clinically sound to let them make the judgment of how much to use. They might get a little uncomfortable if they are unused to or do not like the high, but they will learn and the next time they will be more careful. It will not do anything that is harmful or irreversible.

LG: While the high may be uncomfortable for some people, it's a very positive experience for others. Once Sativex comes on the market some people who have never used marijuana will start using it and they will be introduced to the cannabinoids as therapeutic substances. Unless there is a lot of distance between the dose necessary for the treatment of their symptoms and the psychoactive dose, which for most symptoms I do not believe there is, many if not most patients will get some experience of the cannabis high. Then some may think, "Well, this must be the psychoactive effect, but it isn't so bad; in fact, I have this slight consciousness altering effect and I find it interesting. I feel better, I have better appetite." They may find these effects intriguing and be emboldened to try using herbal marijuana, even smoking it with or without a vaporizer.

There may be a lot of patients who will be introduced to cannabis courtesy of Sativex, who will then judge for themselves which is better for the treatment of their particular symptom. Which is quicker in onset, which is easier to control, which is less expensive? One can imagine that some of them will abandon Sativex, once they try it, in favor of herbal marijuana. On the other hand there will be people who smoke herbal marijuana now and come to believe that an oral preparation, particularly because of the longer duration of effect, would be easier and more useful for their particular symptom. And it is legal! They may try Sativex and discover that, for one reason or another, it works better for them.

That would be great as long as these two approaches were competing on a level playing field. The most important thing that Sativex has going for it, that herbal marijuana does not, is that it will not be illegal to use. That may be a reason why some people for whom it does what they seek with respect to the high will use it for other than medicinal purposes. What troubles me most is that GW insists that there is a world of difference between the medical value of these two substances and the approaches to their use. I believe that if the two substances were matched in the usual capitalist way - nose to nose, may the best product win - I would not like to be an investor in GW Pharmaceuticals because I think that the net effect of this product is going to be negative both with respect to its relative usefulness as a medicine and the task of trying to do something about this insane prohibition.

Already we see that GW has hired Dr.Andrea Barthwell, (formerly the Deputy Drug Czar for the Bush administration's Office of National Drug Control Policy), to promote the acceptance of Sativex in the US. She is a promoter of the widespread view that cannabis use, that smoking marijuana must be extinguished at any cost, even at the cost in my country of arresting about 750,000 mostly young people a year. I expect that she and the people who hired her at GW are going to keep making the claim that the Sativex extract is less harmful than smoked or vaporized herbal marijuana and does not have psychoactive effects until the empirical data to the contrary overwhelm them.

LG: Exactly. Whether herbal marijuana is more effective, or cheaper or less uncomfortable or for whatever reasons people find this is a better medicine, they're going to use it. The question is how much of a legal price are they going to pay for this? Some are put in the situation of having their jobs jeopardized if they use medical marijuana. The reason a lot of patients use Marinol is so that when they get hit with a urine test they can flash a copy of their prescription. To a greater or lesser extent, the same will be true of Sativex. Just as in an indirect way Sativex will be supportive of the prohibition, it will also be used as a dodge to get around the legal system.

LG: I first wrote that in "Marijuana: The Forbidden Medicine" in 1993. Alexander Fleming first discovered penicillin in 1928. He had inadvertently left out an empty Petri dish when he had gone off on vacation and when he returned he found that it had become overgrown with staphylococci; and right in the middle there was a colony of mold. The mold had excreted a substance which was toxic to staphylococcus; that substance was later called penicillin. He published this in 1929 but nobody paid any attention to it until 1941 when two people, Howard Florey and Ernst Chain, took it down from the shelf. They were motivated by the fact that we were now involved in WWII and were on a frantic search for antibiotics. They tested it in six patients, and found how remarkably effective it was against these infections. It was soon clear that in addition to being an amazingly effective and versatile antibiotic, it was remarkably non-toxic and inexpensive to produce. It soon became known as the "wonder drug" of the 1940s. One can't help but wonder how many lives might have been saved from 1929, when the paper was first published, until 1941; that's more than a decade.

So there is no question in my mind, that we have delayed a long time and have denied many people a medical boon. In fact that's the first thing I thought of when my son was suffering from acute lymphocytic leukemia. When I saw how it freed him of the nausea and vomiting of cancer chemotherapy and its terrible anticipatory anxiety, how instead of starting to vomit immediately and having dry heaves for over eight hours, he would now get off the gurney and say, "Mom, can we go get a sub sandwich?". I began to wonder how many other people, how many other youngsters who have to go through chemotherapy could be spared this terrible nausea and vomiting? So for this family it certainly was something like penicillin. It was a wonder drug for us.

LG: Yes, we have lost sight of the importance of freedom of choice with regard to marijuana. There is no risk with marijuana that I know of that justifies denying its use to adults for any purpose. A pernicious thing about the development of Sativex is that the Home Office was apparently persuaded some years ago with an argument that went something like this: "We all know that marijuana has medicinal properties, but we at GW Pharmaceuticals have a way of making it available to patients without burdening them with the two major toxic effects -- smoking and psychoactivity."

These people are trying to hijack the medicinal properties of cannabis toward their end of selling a product which they claim will be safer (because it will be free of these two "serious" toxicities) than herbal marijuana. This is consistent with the aggressive PR campaign which is a major part of Sativex. Unless you can make the claim that crude herbal cannabis is very different from and more toxic than Sativex, how can you justify hiring Dr.Andrea Barthwell as spokesperson for the promotion of this substance? She says there is no medical utility in marijuana, that medical marijuana is a hoax. She is the insistent author of these statements and now she is promoting Sativex. Hiring her is consistent with this sort of schizoid approach to cannabis: in this form it's good; in that form it's bad; in this form, everyone who has these symptoms should try it; in the other form, people should be punished for using it as a medicine.

LG: That is a difficult question. It is hard to believe that with her training as a physician, and considering her past and present positions that she hasn't looked carefully and critically at the literature on medicinal cannabis, including the large amount of anecdotal data. I would have expected her to have achieved a better understanding of this whole problem. That they hired her is as cynical as her acceptance of the job. It's a measure of the lack of integrity that GW Pharmaceuticals is involved in when they try to make the case; orange juice, yes, oranges, no, they're bad.

When I talked about pharmaceuticalization in the past, as a starting point I made it clear that there were some wonderful things that would come out of the attempts to develop pharmaceuticals from marijuana. I specifically mentioned, as an illustration of these possibilities, that the development of an inverse agonist to the "munchie" effect, the appetite stimulating property, might actually produce something that we have failed to develop in all these years, a non-toxic weight control substance. The other side of the pharmaceuticalization coin was my concern that the government would see pharmaceuticalization as a way of dealing with its problem with medical marijuana; .i.e., how to enable its use for medicinal purposes, while at the same time prohibiting it to people who want to use it for other purposes. In 1985, the government mistakenly thought the problem was solved when a small pharmaceutical company called Unimed developed the medicine known as Marinol (dronabinol) which is synthetic THC. That is exactly the same chemical you find in herbal marijuana and Sativex.

LG: It's very expensive to develop a new drug and the cost is borne by the drug company which develops it. However, in this particular case the US government supported its development, but insisted that it be encapsulated in sesame oil so it could not be smoked. They went so far as to assign this THC (Marinol) not to Schedule 1 alongside its identical twin, the THC which is the most prominent cannabinoid in herbal marihuana, but to Schedule 2 so it could now be prescribed, and a few years later to the even less restrictive Schedule 3. But THC by any other name is THC. This is so hypocritical. This was the government's attempt to say, "Don't keep pushing for marijuana as a medicine; now there is a cannabis medicine; it's called dronabinol or Marinol. Buy it at your local pharmacy." Now this gives them a reason not to allow marijuana as a medicine, a goal they are pursuing with the full power of the federal government in California as they vigorously attempt to close down the compassion clubs. Sativex will be used as another tool in this attempt at the pharmaceuticalization of marijuana. A cynic might say it was designed for this purpose. The US government may very well adopt it because it gives it another preparation in this armamentarium which allows it to say, "Look, there is now another cannabis medicine out there. There is no need to give special license to people who want to smoke marijuana as a medicine when they can now get what they need through these other medicines." So the government can be expected to be supportive of any pharmaceutical company which develops a substance that can compete with marijuana. And self interest would suggest that these pharmaceutical companies would be sympathetic to the US government's goals of suppressing the use of herbal marijuana, both as a medicine and in general.

LG: It's as though the modern media exchanged the stereotype of the lascivious killer marijuana smoker of Reefer Madness for the Cheech and Chong stereotype. You and I as well as most people who use marijuana no more conform to that stereotype than we did to the Reefer Madness stereotype. The way I'm trying to deal with that is through my Uses of Marijuana website (www.marijuana-uses.com) which is a series of essays. Some of the many contributors are well known, like Allen Ginsberg and Carl Sagan, but most of the contributors are unknown and some use pseudonyms. I continue to seek essays from people who use marijuana for non-medical and non-recreational purposes and have found that it plays some significant role in their lives.

You can't read these essays without thinking, "Hey, these are solid citizens who are accomplishing things in their lives and who are using it for purposes I never dreamed of." Here's an e-mail about the web site which I received this morning: "Dear Dr. Grinspoon: There is a real need to discuss the positive side of cannabis (does the public know there is one?) and this seems like an excellent way to do it. I will make a point of writing [an essay for this web site] when I have completed my PhD this summer, much of which could not have been done without cannabis as a creative tool and medicine. By the way, as a young scientist, I have been inspired by and learned many lessons from Carl Sagan's work and the ways in which he, you, and many others have taken the risk to write about cannabis, and this knowledge is not lost on our generation. I'm currently looking forward to doing my Post Doc on particular cognitive processes while performing real work tasks under the influence of cannabis, some of which I expect to be very positive. Best regards."

Some decades ago a courageous psychiatrist by the name of Richard Pillard at Boston University was the first contemporary notable gay man to come out of the closet. That started the "out of the closet" movement. We are a long way from defeating homophobia in this country but we've made great strides since people have started coming out. Pillard, Barney Frank and various others have helped people understand that this isn't some sort of toxic mental disorder that you have to be frightened of or scorn. Similarly I think many have come to understand that folks like us are successful people, we do not develop extra heads or what have you. In fact let me tell you, it's been most useful to me in going about my life.

LG: Well, I think it is because the government, for whatever reason, is afraid that as people get more experience of marijuana through observing people who use it as a medicine, they will be more tempted to use it for purposes that the government disapproves of. If you see your Aunt Nellie using it to treat the effects of chemotherapy or a friend who uses it to treat convulsions much more successfully than with conventional medications, you may come to change your mind and say, "Wait a minute, what's all the fuss? This seems to be a perfectly respectable application of herbal medicine and it appears to be quite benign. So what if it's used for other purposes? Nothing harmful happens; it doesn't seem to be having any kind of a deleterious effect on these people." Let me tell you a story which illustrates this type of change in attitude.

A colleague I worked with at the Harvard Medical School called me one day after he had skimmed through "Marijuana: The Forbidden Medicine". His mother-in-law had developed pancreatic cancer and was having a lot of trouble with nausea. "That medicine you mentioned in your book, Marinol, would that help her and would it be safe to give to a 67 year old woman?" he asked. I told him it was quite safe and that it probably would help her, but there was a better way to do it with more prospect of success than taking this oral preparation. I suggested that she find someone who would teach her how to smoke marijuana. "I would never have my mother-in-law do that", was his reply. So I told him what to do with respect to taking Marinol and suggested that he give her my telephone number to use if she had any difficulty. Two weeks later, I got a call from this 67 year old woman who told me that the Marinol worked at first, but its effectiveness had diminished considerably. She had raised the dose but its usefulness continued to decline. "What should I do?" I asked if she knew anyone who could teach her to use marijuana. She said, "Yes, I have a grandchild in college and she's been urging me to smoke marijuana for a long time." I said, "Okay, here's what you should do: have her show you how to roll a joint and to smoke with you the first few times. Just take one puff and wait two or three minutes at least, and then if you feel nothing, take another puff and wait. Keep doing this until one of two things happen: you start to feel uncomfortable and anxious, or you start to get symptom relief. At that point stop."

A while later, during a meeting at the office of this associate, he asked if I could stay for a few minutes after the meeting. His mother-in-law was now living with them in their Boston suburban home. "I can't tell you how thankful our family is to you," he said. He went on to tell me how his three boys (all in their 20s and all quite successful) would roll a joint with Granny, sit around, share a smoke and have the best time. Her nausea was now controlled and she had begun to eat again. "It was unbelievable." Several months later she died. When we arrived at their annual Christmas party his wife greeted us at the door and said in almost identical words, "I can't tell you how indebted we feel to you!" She repeated the story of how it made all the difference in her mother's last couple of months; free of the nausea she perked up remarkably and had a much more fulfilling last few months. And the family, of course, was relieved at not having to see someone they loved suffer with such discomfort.

She also said; "When my boys were in college and I learned that they were smoking marijuana, I came on like a banshee and really put my foot down." In retrospect, it embarrassed her, and she went to on to ask, "And that is what the government is afraid of?" A growing number of people are having and will have similar experiences, and they will see for themselves that they have been lied to for years. And there will grow a pressure to stop arresting people who use marijuana as a medicine, if not to reverse the prohibition altogether. Medical marijuana is going to teach people that this substance is not the demon that the government has been describing for years.