Cannabis As A Mood Stabilizer In Bipolar Disorder
CANNABIS AS A MOOD STABILIZER IN BIPOLAR DISORDER
by Lester Grinspoon MD, Associate Professor of Psychiatry, Harvard Medical School
Thirty to 40% of patients with bipolar disorder are not consistently helped by or cannot tolerate standard medications. In the course of our studies of the medical uses of cannabis, we have discovered a number of sufferers who believe it to be more effective than conventional anti-manic drugs or use it to relieve the side effects of lithium (1). Here’s one example:
I am a thirty-five-year-old woman with severe manic depression. When I was growing up I was hypersensitive, cried all the time, and fought with my brothers and sister. My parents always said they had to handle me with kid gloves. I had more energy than most and used it to the hilt. I was an agile gymnast and one of the fastest swimmers in my school. I was also at the top of my class in algebra and good at art and creative writing. I used to stay awake at night and dream up stories.
Around age fourteen my mood swings began to get more intense. I was agitated, restless, and constantly fighting at home. I lay awake at night and lost a lot of weight. Eventually I snapped and was sent to a mental hospital, where I was diagnosed as having manic-depressive disorder. They put me on lithium and told me I would have to take it the rest of my life. But lithium made me lethargic. I had trouble communicating and lost all my animation and creativity. Eventually I quit taking it. Recently I have also tried carbamazepine and valproic acid, neither of which helped. Carbamazepine started a manic episode, and valproic acid had some very bad side effects. I'd like to find something else, but I don't have health insurance or the money to spend trying out new medications.
Since the age of fourteen I have had manic episodes regularly about once every six months. It would always start with not being able to sleep or eat. After two weeks I would just break down and seem to trip out into another world. Usually I ended up in a mental hospital.
I smoked marihuana for the first time in high school and couldn't believe how good it made me feel. My normally chaotic emotions subsided and I had a sudden sense of calm, peace, and well-being. My perceptions of others and life changed dramatically. The world no longer seemed hostile but more within my control. I could sleep easily and actually had cravings for food. There were practically no side effects. When I had enough marihuana I would just naturally stop, because once you've gotten a certain effect you really don't want any more.
Only another manic-depressive using marihuana could possibly know how much this has changed the quality of my life. Although they don't know it, my family actually likes me better when I'm stoned than when I'm taking lithium or not taking anything. When I'm stoned they can predict my moods and actually get close to me. But I can't tell my family or the doctors because it's illegal. I have to live a double life to get along.
I've often tried to quit marihuana, but I have a manic episode every time. Last year I decided I could control my emotional ups and downs without marihuana, but it led to one of the worst episodes I've ever experienced. I had been having trouble sleeping as usual. I began to get super clear vision that a disastrous earthquake was going to hit Los Angeles. I was feeling so good I was sure I was right. Soon I had my roommate convinced that we didn't have much time and would have to buy as many supplies as possible and then leave. We thought that after the quake the New World Order would be implemented and everyone would have to take the number that Revelations talks about in the Bible. We planned to go to El Salvador, where her family lives, and hide out for the next three and a half years. Crazy! But I really believed it. I maxed out all my credit cards, quit my job, and packed up all my things, including disguises I thought we were going to need. Eventually I had to return home with no job and major bills.
I knew then and there that I would have to go back on marihuana. It's been seven months now since I resumed smoking marihuana, and I don't know what else to do. I have to choose between obeying the law and staying sick or breaking the law and being well.
In some ways cannabis today is in a position analogous to that of lithium in 1949, when J. F. J. Cade, after observing its sedative effect on guinea pigs, administered it to patients suffering from "chronic and recurrent mania." His seminal paper, "Lithium Salts in the Treatment of Psychotic Excitement," presented ten one-paragraph case histories, and this compelling anecdotal evidence attracted the attention of psychiatrists around the world because there was no adequate treatment for bipolar disorder. In his paper Cade mentioned the need for "controlled observation[s] of a sufficient number of treated and untreated patients" (2). In 1951 Noack and Trautner followed up by reporting on the treatment of another thirty patients with "mania alone." But they pointed out that not all patients improved, that many discontinued the treatment, and that "it does not appear to be justified to accept the lithium treatment of mania as invariably safe" (3).
In 1954 M. Schou et al published a controlled study in which they alternated lithium and placebo at two-week intervals. Lithium was clearly beneficial for twelve patients; fifteen showed improvement that was "not as clear-cut," and three did not improve at all. Schou and his colleagues found it "rather astonishing that [lithium's success] has failed to arouse greater general interest among psychiatrists." One explanation they offered was its low therapeutic ratio. Another explanation was "the difficulties encountered in attempts to convey to others in a quantitative manner...the effect of a new psychiatric therapy," i.e. to move beyond anecdotal data to controlled studies (4). But there was an even more compelling reason for the delay in lithium's acceptance in the United States. In this country, drugs are introduced by pharmaceutical companies which invest in the studies necessary for official acceptance. They do this because they receive a patent (in the 1950s, for seventeen years) on the new drug which allows them to recoup their investment. Lithium salts, of course, could not be patented.
Similar obstacles face the medical use of cannabis today. Lithium had a reputation for toxicity that grew out of its use as a salt substitute for cardiac patients in the 1940s. There were a number of deaths before its dangers were fully appreciated, and today blood levels are carefully monitored. Because of its non-medical use, cannabis also has a reputation for toxicity, in this case undeserved. Lithium was unpatentable, and so is cannabis. Finally, like the evidence for lithium in 1949, the evidence for the therapeutic value of cannabis in bipolar disorder today is anecdotal. Although it has been repeatedly considered as a treatment for affective disorders in the Western medical literature since 1845, when Jacques- Joseph Moreau de Tours recommended it for melancholia, there is little in the medical literature on the use of cannabis as a mood stabilizer (5,6,7,8).
Today drugs must undergo rigorous, expensive, and time-consuming tests to win approval by the Food and Drug Administration (FDA) for marketing as medicines. The purpose of the testing is to protect the consumer by establishing both safety and efficacy. First the drug's safety (or rather limited toxicity) is established through animal and then human experiments. Next, double-blind controlled studies are conducted to determine whether the drug has more than a placebo effect and is at least as useful as an available drug. As the difference between drug and placebo may be small, large numbers of patients are often needed in these studies for a statistically significant effect. Because no drug is completely safe (non-toxic) or always efficacious, a drug approved by the FDA has presumably satisfied a risk-benefit analysis. When physicians prescribe for individual patients they conduct an informal analysis of a similar kind, taking into account not just the drug's overall safety and efficacy but its risks and benefits for a given patient and a given condition. The formal drug approval procedures help to provide physicians with the information they need to make this analysis.
But devotion to formal procedures may have caused us to undervalue anecdotal evidence. Regulators today are willing to accept the experience of physicians and patients as evidence of adverse effects but not as evidence of therapeutic effects (9). Yet case histories and clinical experience are the source of much of our knowledge of synthetic medicines as well as plant derivatives. Controlled experiments were not needed to recognize the therapeutic potential of chloral hydrate, barbiturates, aspirin, curare, insulin, or penicillin. More recently, the uses of propranolol for angina and hypertension, diazepam for status epilepticus, and imipramine for childhood enuresis were discovered in the same way, although these drugs were originally approved by regulators for other purposes.
A related source of evidence is the experimental method known as the N of 1 clinical trial or single-patient randomized trial. This is the kind of experiment used by Schou and his colleagues, in which active and placebo treatments are administered in alternation or succession to a patient. The method is often used when large-scale controlled studies are impossible or inappropriate because the disorder is rare, the patient is atypical, or the response to treatment is idiosyncratic. We have encountered several patients with bipolar disorder who carried out somewhat similar experiments on themselves. They alternated periods of cannabis use with periods of no use and discovered that cannabis was effective.
The familiar deficiency of anecdotal evidence is the risk of counting successes and ignoring failures. If many people suffering from clinical depression take, say, St. John's wort after unsuccessful treatment with conventional antidepressants and a few recover, those few stand out and come to attention. Bipolar disorder is a cyclical condition, so it is essential to avoid confusing natural remission with drug-induced improvement. At present we do not know how many patients with bipolar disorder would benefit from cannabis. The promising anecdotal evidence points to the need for more systematic clinical investigation, just as it did 50 years ago in the case of lithium.
Thousands of years of widespread use as well as recent research designed to discover toxic effects have made it clear that cannabis is an unusually safe drug. In fact, its long-term safety is better established than that of St. John's wort. Yet unlike St. John's wort, cannabis would be subject to government regulations that demand further time-consuming and unnecessary safety tests. The classification of cannabis as a Schedule I drug creates further obstacles to clinical research. But given the disinterest of pharmaceutical companies, there is no immediate prospect of such studies being funded even if the political obstacles are removed. We are left with the tantalizing possibility that cannabis (or one or more of its constituent cannabinoids) is useful in the treatment of bipolar disorder and the sad knowledge that in the present circumstances little can be done to explore that potential.
1. L. Grinspoon and J. B. Bakalar, Marihuana, the Forbidden Medicine, Revised and Expanded Edition (New Haven: Yale University Press, 1997).
2. J. F. J. Cade, "Lithium Salts in the Treatment of Psychotic Excitement," The Medical Journal of Australia (Sept. 3, 1949): 349-352.
3. C. H. Noack and E. M. Trautner, "The Lithium Treatment of Maniacal Psychosis," The Medical Journal of Australia (August 18, 1951): 219-222.
4. M. Schou, J. Juel-Nielsen, E. Strömgren, and H. Voldby, "The Treatment of Manic Psychoses by the Administration of Lithium Salts," Journal of Neurology, Neurosurgery and Psychiatry 17 (1954): 250.
5. J.-J. Moreau de Tours, "Lypemanie avec stupeur; tendance à la démence.--traîtment par l'extrait (principe resineux) de cannabis indica--Guérison," Lancette Gazette Hôpital 30 (1857): 391.
6. G. T. Stockings, "A New Euphoriant for Depressive Mental States," British Medical Journal 1 (1947): 918-922.
7. D. A. Pond, "Psychological Effects in Depressive Patients of the Marihuana Homologue Syndexyl," Journal of Neurology, Neurosurgery and Psychiatry 11 (1948): 279.
8. C. S. Parker and F. W. Wrigley, "Synthetic Cannabis Preparations in Psychiatry: I. Synhexyl," Journal of Mental Science 96 (1950): 276-279.
9. L. Lasagna, "Clinical Trials in the Natural Environment," in Drugs Between Research and Regulations, ed. C. Stiechele, W. Abshagen, and J. Koch-Weser (New York: Springer-Verlag, 1985): 45-49.
FINANCIAL DISCLOSURE: no conflicts