Dr. Danovitch: The answer depends whom you ask. If you ask patients who consume marijuana or individuals in the public, they cite a wide variety of different conditions for which they feel that marijuana is helpful, including chronic pain conditions, a variety of mental health disorders, sleep disorders, neurological problems, some cancers, spasticity and the list goes on. The symptoms for which there has been the most evidence include nausea and vomiting, alterations in appetite, and muscle spasticity, and there have been some impressive reports of anticonvulsant and analgesia effects. In labs, cannabinoids have been shown to have immunomodulatory properties and impact on cancer growth (Hall WL et al, Lancet Oncol 2005;6(1):35–42).
TCPR: Those who use marijuana typically inhale or ingest the leaves and buds of the Cannabis sativa plant. Does there seem to be any difference in terms of therapeutic efficacy of the whole plant versus individual cannabinoid compounds?
Dr. Danovitch: There have been studies that have shown efficacy of the whole plant, and there is also evidence that individual constituents, like cannabidiol, have significant therapeutic potential. There are 60 cannabinoids in the whole plant and probably another 400 different hydrocarbons. In the lab, we can purify cannabinoids, or study synthetic cannabinoids or cannabinoid modulators, and try to understand what they are doing. But studying them individually doesn’t replicate what they do together in the context of the whole plant. On the one hand, pharmacological purists would say we will never have standardized, consistent, high quality preparations of cannabinoids until we are able to produce them reliably, regulate them, and know exactly what their effects are. On the other hand, many advocates of “medical marijuana” say that it is exceedingly difficult to replicate whole plants, and the whole plant may have sufficient benefit that it should be studied independently from efforts to isolate therapeutic compounds. I would say that both positions and
perspectives have some merit.
TCPR: Patients often talk of the differences between the two strains of marijuana, C. sativa and C. indica. Is there any evidence showing that they differ in their therapeutic potential?
Dr. Danovitch: Well, there are almost certainly differences because patients or individuals who use them can identify clear differences in the intoxication syndrome and effects. The ratios of THC to cannabidiol and to some of the other phytocannabinoids are different; they vary across different strains and subspecies. Right now, there is a lot of effort to cultivate strains that are higher in phytocannabinoids, which are thought to be more therapeutic, but we don’t have any way of really knowing because these processes aren’t well standardized. There is a long history of incredible ingenuity in science and agriculture of farmers trying to cultivate species of products for the tastes of the consumers. And whether it is really red, tasty tomatoes or marijuana plants that have certain effects, it’s the same process. It is kind of like a guerrilla science of individuals trying to figure this stuff on their own.
TCPR: What do we have for data on long-term benefits or risks of using marijuana for certain medical conditions?
Dr. Danovitch: Ultimately, there are really more questions than answers in terms of how effective marijuana is both in the short term and in the long term. Patients and individuals are much more capable in general of identifying and detecting short-term effects of an intervention than long-term effects. And so there is a disparity between the recognition of short-term alleviation of symptoms, and the question of how marijuana or its constituents impact disease progression and health outcomes in the long run.
TCPR: Why is it difficult to study marijuana? Why do so few labs use marijuana in clinical research?
Dr. Danovitch: The DEA, with input from the FDA, schedules drugs into five different categories. Schedule I means that a drug has high abuse potential, is unsafe and has no accepted therapeutic benefit. Schedule II means that there is high abuse potential, but some therapeutic benefit. Marijuana is placed in schedule I. There have been a number of calls to have it moved into schedule II, because it is easier to study medications that are in schedule II. While it is possible to study agents that are in schedule I, there is a pretty rigorous federal regulatory process to navigate. Critics, including several major professional associations, have pointed out that the current scheduling designation has made it difficult to conduct research because only a handful of labs with the right infrastructure can be successful in getting approval to study marijuana.
TCPR: Is it clear how addictive marijuana is?
Dr. Danovitch: About nine percent of marijuana users go on to develop a marijuana use disorder; which means that about 91 percent don’t develop any problems related to marijuana addiction. This illustrates the point that it is not just a property of the substance that determines who develops a substance use disorder on cannabis or anything else. It is properties of the individual, of their biology, of their genetics, and also multiple psychosocial factors, such as their development, their psychology, and their environment.
TCPR: How about the risk of psychosis?
Dr. Danovitch: The majority of people are not at heightened risk for developing a psychotic disorder with the use of marijuana. However, for the one or two percent of the population that may have a vulnerability to develop a psychotic disorder, marijuana may double the risk that they actually will (Moore THM, Lancet 2007;370(9584):319–328). While two percent may sound like a small number, given the prevalence of marijuana use, the number of people potentially impacted is significant.
TCPR: Are there any screening tools or genetic profiling that could be done to sort out those who are more susceptible to the longer-term consequences of marijuana use?
Dr. Danovitch: Well, there are some specific genes like the COMT [catechol-O-methyltransferase] gene that has been associated with psychosis. But practically speaking, anybody who has a family history of schizophrenia or a psychotic disorder is somebody whom I really carefully educate about the risks of marijuana in creating and contributing to psychoses. Certainly, anybody who has a family history of a substance use disorder is at risk of developing a substance use disorder, and anybody who is young and whose brain hasn’t finished developing is at higher risk of the cognitive problems associated with using marijuana, especially if they smoke heavily. I really try to take time to educate marijuana users about the profile of the substance so that they can make an educated decision about it, and also try to understand what it is doing for them, because everybody uses for a reason, and without understanding what that reason is it is really hard to actually help them with it.
TCPR: Are there distinct risks related to the age at which someone starts smoking marijuana?
Dr. Danovitch: Yes. The risk of harm associated with marijuana is highest among children and adolescents. Marijuana appears to have subtle but distinctive effects on brain development. We know that the brain finishes developing in the mid-20s. Studies that have looked prospectively at marijuana’s effect on cognitive function have found that their findings hinged on marijuana being used prior to the age of 18. So, for instance, the Dunedin study found that the adverse effects of marijuana on IQ only happened among people who started smoking marijuana prior to the age of 18, and were not found in those that started smoking marijuana after the age of 18, irrespective of whether they met criteria for marijuana use disorder (Meier MH et al, Proc Natl Acad Sci USA 2012;109(40):E2657–E2664). At the same time, researchers have characterized wide-ranging trajectories of marijuana use. Some people start smoking really early on and progressively increase over the course of their lives. Other people start smoking and use heavily during their college years, but then stop after college. Some people smoke small amounts throughout their lives. And so, not surprisingly, there are differences in outcomes as a function of how heavily people use, how early they use, and other contributing factors. So earliness of use matters, quantity of use matters, and then existing vulnerabilities, both physiological and environmental, matter as well.
TCPR: As marijuana becomes more accepted and more legalized, how can we preserve the well-being of people who may suffer from the negative consequences of marijuana?
Dr. Danovitch: First, treatment works, but it can only work if it is accessible. We have to ensure that individuals who develop marijuana use disorders, particularly adolescents, have access to quality treatment. Second, we need appropriate safeguards. There have to be effective restrictions minimizing access for underage individuals. And, there needs to be a regulatory system to protect users by implementing quality controls, using warning labels, and preventing inappropriate marketing. Third, if there’s going to be a major policy change, there needs to be a mechanism to study its effects. Across the country there are many different initiatives that have increased availability of marijuana, and this has happened faster than our ability to systematically analyze the public health impacts of these changes. This deserves further study. And then, there are a number of technical challenges like documenting driving under the influence that have yet to be sorted out.
TCPR: And there’s an idea that funding for these programs could come from earmarking revenue, from taxing marijuana for example.
Dr. Danovitch: Yes, there is a notion that any revenues that might be generated from taxation should first be designated to address public health problems associated with marijuana. However, there is also concern about the feasibility of appropriating funds for that purpose—if you look at alcohol or tobacco, big business has tended to be far more successful than public health advocates in controlling taxation and appropriation. Several medical societies are concerned about the public health effects and are trying to educate the public about it. The question is, how can we inform our legislators so they can appropriately govern and protect the public health with respect to this issue? And the wariness is that no matter how much we beat the drums on the risks, that the influence of big business interests on government will be greater than the impact of public health and medical interests on government.
TCPR: Let’s say that you are a psychiatrist somewhere in a state that permits the medical use of marijuana. If a patient comes to you with a psychiatric complaint and inquires about medical marijuana, what kind of approach do you take?
Dr. Danovitch: I would start by assessing the complaint itself, making a diagnosis, and recommending treatments based on existing evidence. At this point in time I have not seen any high-quality studies demonstrating that marijuana is effective for any psychiatric diagnoses. And a lot of the symptoms that
patients report marijuana is helpful for—like reduction in anxiety, improvement with sleep, reduction in irritability or quickness to anger, and enhancement of appetite—these are all things that are associated with marijuana withdrawal, too. As a result, it is often difficult to disentangle the patient’s perception of marijuana benefits from the possibility that they may just be treating their own withdrawal symptoms and experiencing alleviation of symptoms on account of that. Ultimately as a psychiatrist, I really can’t think of any psychiatric condition for which I would recommend marijuana.
TCPR: Thank you, Dr. Danovitch.