Marijuana use is legal in many states for medical purposes, most of them dealing with neurological conditions (pain, epilepsy, tremor, multiple sclerosis, and many others). From the perspective of a neuroscientist researcher, the situation with respect to “medical marijuana” is absurd.
I watched as the young woman inhaled the pungent smoke deeply into her lungs and held it for a second. Clouds of blue-gray smoke exploded from her mouth and nose in a series of short violent coughs. “Sorry, this strain is kind of harsh,” she said.
Rebecca, a bright graduate student at one of the nation’s leading universities, was eager to demonstrate to me the immediate medical benefit marijuana provided her. Out of respect for her privacy, I will not delve into the specific neurological condition Rebecca had discovered was improved by the use of marijuana; moreover, the issue here is much larger than any one condition. The issue is the absurdity of current regulations on medical marijuana and the profound injury these laws are causing thousands of people, while fortifying a wall of ignorance that neuroscientists cannot easily surmount.
Rebecca has a legal prescription to use medical marijuana for her condition, which she administers by vaporizer. The condition Rebecca is using medical marijuana to treat by self-medication is chronic, serious, and there is no drug available to treat it. Rebecca has scoured the medical and neuroscience literature, and collected compelling scientific evidence for the possible benefit of marijuana for this condition, based on the expression of CB1 and CB2 cannabinoid receptors in the appropriate neural circuits involved. (These are the receptors on cell membranes that are stimulated by the active components in marijuana.) The problem is that the legal restrictions on studying marijuana in people are so arduous or impenetrable, that performing the simple experiments that would advance scientific knowledge and could lead to powerful new treatments for disease are nearly impossible.
Thankfully the horrors of the past when medical experiments were sometimes performed on people without their full knowledge and consent are gone. (In most countries.) All research involving human subjects in the United States must be reviewed and approved in advance by an independent review board that carefully weighs the risks and benefits to ensure that the experiments are ethical, scientifically warranted, and conducted properly to protect the health and interests of the person volunteering to participate in the study. This is a rigorous process and it should be.
The problem is that the laws regulating marijuana in some states, as well as federal laws, make it impossible or nearly impossible to do research on the biology of marijuana and its potential medical benefits. The PhD advisor of a graduate student I know laughed at him when he proposed to study the neuroscience of marijuana addiction in rats, because it would be so difficult to obtain the active ingredient in marijuana (THC) for experimental research. The mentor advised his student that he would be far better off to change his research to study cocaine. He did so.
A colleague of mine, a well-known expert on hippocampal synaptic function, became interested in what appeared to be a possible significant role of CB1 cannabinoid receptors on neurons in regulating development of a particular type of neural circuit. “Getting the clearance to work with THC was impossible,” he told me. The studies he proposed were on experimental rats not people, which is far less arduous than obtaining permission to do experiments on people. Undaunted, the researcher found a synthetic analog of THC that was unregulated, but was actually far more potent than THC, and he began his studies with this compound. Such cleaver circumvention of the restrictive laws on cannabinoids in experimental research are rarely possible. Moreover, any results obtained will have to be tested eventually with real marijuana, a plant that contains 60 different cannabinoids in various mixtures and concentrations that vary greatly in different plant strains.
In Rebecca’s case, the ethical issues related to studying the neurological effects of marijuana would seem much less problematic, because she has a legal prescription to use marijuana for her condition. The research would not subject her to additional risk; it would simply examine the biological effects on the patient of the currently prescribed medication. However, the researcher with the expertise to examine the effects of marijuana on her condition works at a University in another state where marijuana possession is a crime. The researcher has vigorously pursued the appropriate avenues to undertake this experiment, but it is not possible. The time and effort to gain approval to do the research are insurmountable obstacles, given the investigator’s other research responsibilities. Moreover, the judgment of officials familiar with such approvals are that regardless of the scientific merit and ethical justification for doing the research, marijuana is illegal in that state. The research could not be done there. Similarly, federal law criminalizes marijuana use, even for medical purposes, and most biomedical research is funded by federal grants.
A recent survey of the medical literature on the benefits of marijuana for the wide range of neurological conditions (published this year in the journal Neurology) found 34 studies performed between the years 1948 and 2013 that met their criteria for inclusion. Stop right there. 34 studies! Only 34 studies were found for the enormous range of neurological conditions where activation of CB1 and CB2 receptors in the brain by compounds in marijuana could have an effect? There are 32,836 studies in the scientific literature on “health and tobacco.” There are 87,735 studies on “health and alcohol” in the medical literature (PubMed search). The authors reviewing the scientific literature on marijuana found only a total of 1729 studies in the literature, but only 34 studies since the Truman Administration met the criteria to be useful for inclusion in an analysis of the efficacy of medical marijuana on neurological conditions. The criteria for inclusion required that the studies were well-designed, randomized, with placebo-controls, performed on humans; not anecdotal reports,human studies without controls or animals studies.
It is not the scientific rationale for possible effects of marijuana on neurological conditions that can account for the lack of research: the effects of marijuana on the central nervous system are obvious and potent. It is not a lack of interest among researchers in studying how CB1 and CB2 receptors regulate development and function of the brain, and how this new knowledge could lead to new drugs for treating disease and human suffering. The difference is that alcohol and tobacco are legal; marijuana is not.
Tobacco, alcohol, and morphine, are all plant products, just like aspirin. All life on this planet shares a common system of biochemistry. Compounds in plants have powerful effects on the human body, some are poisonous toxins and some are priceless cures. Plants have yielded a treasure trove of potent new drugs that have treated or cured diseases throughout human history, and eased human suffering. New drugs have been developed from plants that have changed the world. Oral contraceptives were developed from a jungle plant, leading to a technological development that has helped countless women with many medical conditions and transformed the lives of women and society by putting women in control of the biological systems at work in their own bodies. But marijuana is off limits.
Science is strangled by a government-imposed catch-22 that restricts access to marijuana on the basis that there is insufficient evidence supporting its medical benefits and safety, while blocking the research that would provide such information.
So we have this absurd situation where the use of medical marijuana is legal in 22 states, yet the scientific research that would uncover the molecular mechanisms by which this plant can treat a wide range of medical conditions is impossibly difficult to perform. In states where the drug is illegal, research is all but impossible. Businessmen decry onerous government regulations that hamper commerce and diminish financial profit, but there the losses are investor’s dollars not people’s lives to disease.
With 60 known cannabinoids in this plant, and the mixture and potency varying widely among strains and from batch-to-batch, patients are left to self-experimentation to find a strain that works for them. Is it Super Silver Haze, White Widow, Skywalker, or God’s Gift? Who knows? The patient is compelled by law to engage in desperate self-experimentation of the sort that would never be approved by an Institutional Review Board examining a proposed scientific study.
Meanwhile there are countless natural products approved for use and promoted for medical benefits that have dubious efficacy or scientific foundation-- chondroitin sulfate, Gingko, green tea, resveratrol in red grapes, vitamins of every type and in endless combinations--but cannabis is banned, paradoxically precisely because the compounds in it do have obvious and potent effects on the CNS.
Rebecca discovered the beneficial effect of marijuana on her medical condition by chance in using marijuana recreationally, but she does not want to be dependent on it for her medical needs. There are far too many obvious adverse effects. Any potent drug has adverse effects, but without knowing exactly what compound or combination of compounds in marijuana are helping and which are hurting, and without the necessary scientific research to understand the biological facts that would accelerate the development of potent, effective, and safe new drugs, she has no choice. What she wants is to help scientists discover how this drug is working for her, and help them to develop the right drug that will work but not leave her stoned or at risk from other dangerous compounds in marijuana and the very real harmful effects of cannabis if used incorrectly.
So here we are in the 21st century condemned like cavemen to eat leaves or smoke them for medical uses because the legal regulations restricting access to this particular plant for scientific research are so arduous, for political reasons, that we are constrained by law to the practices of witch doctors.
Koppel, R.S. et al., (2014) Systematic review: Efficacy and safety of medical marijuana in selected neurological disorders. Neurology, 82, 1556-1563.
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