UPDATE 4/15 – Judge Mueller denied the motion.
2/11/2015 – Judge Mueller says she will issue her ruling within 30 days.
Depiction of the courtroom scene with Dr. Madras testifying by Ron Mullins.
SACRAMENTO, Oct 29th – The fourth and fifth days of U.S. court hearings before Judge Kimberly Mueller on the constitutionality of marijuana’s schedule one classification was spent in cross-examining the government’s only witness, Dr. Bertha Madras, Professor of Psychobiology at the Harvard School of Medicine. The gravamen of Dr. Madras’ testimony was that marijuana has not met the high standards of proof required for FDA approval. Dr. Madras’ expressed concerns on two issues: (1) the insufficiency of well-controlled, double blind, efficacy trials of natural cannabis and (2) the inappropriateness of smoking as a method of delivering medication.
Dr. Madras criticized the adequacy of published studies by the CMCR (California Center of Medicinal Cannabis Research) showing benefits of smoked marijuana for neuropathic pain and multiple sclerosis, on the grounds that the experimental subjects had been limited to experienced marijuana smokers. Defense Attorney Zenia Gilg asked why, even if its benefits were limited to them, experienced users shouldn’t be able to use marijuana for medicine. “If cannabis is rescheduled, it assumes that everyone will be considered,” Madras replied.
Madras said there were a “lot more weaknesses” with the CMCR studies, among them a lack of long-term safety data, a vague and subjective definition of tolerated side-effects, and other problems. For example, Dr. Abrams’ study on marijuana and weight gain in HIV patients did not show whether the subjects in question actually had reduced morbidity or mortality.
With regards to the smoking problem, Gilg asked whether that wasn’t a special case, since cannabis can also be administered through inhalers, vaporizers, oral preparations, etc. Madras replied that the FDA would need to evaluate alternative delivery methods separately from smoked medication, rendering CMCR’s studies with smoked marijuana irrelevant for approval purposes.
Madras poked holes in other studies, finding them at best “suggestive” but methodologically deficient from the standpoint of FDA approval. She rejected Gilg’s suggestion that there were 100s of studies showing marijuana’s efficacy, estimating that there were only five to ten double-blind, placebo-controlled studies of natural marijuana (as opposed to pure cannabinoids) purporting to show medical efficacy, and that these all had methodological deficiencies and insufficient subject populations.
Gilg pointed to an exhibit of the new drug approval for Marinol (dronabinol) , noting that it cited just a single clinical trial of 139 subjects. Dr. Madras replied that there had actually been 17 studies of Marinol involving 454 patients before its approval, and that FDA would have taken these into account in making its approval decision.
Gilg turned the discussion to CBD. Madras agreed that CBD showed promise and appeared to “antagonize” THC, but that there had been only two or three “very limited” studies with a handful of subjects. Asked whether it was reasonable for CBD to be in schedule one when synthetic THC is in schedule three, Madras was flummoxed, saying she had been unaware that CBD was in schedule one.
Gilg pointed to another witness sitting in the courtroom, Jennie Storms, poignantly accompanied by her 14-year old, wheelchair-bound son, Jackson, who suffers severe, disabling seizures from Dravet’s syndrome. Finding that her son’s condition could only be alleviated with CBD-rich marijuana, Storms decided to move to Colorado from New Jersey in order to gain access to medicine. “Should we consider THC/CBD combination medication for patients like Jackson, yes or no?” asked Gilg. “No” answered Madras.
Madras went on to agree that CBD and other cannabinoids are “promising medication,” but that further studies are necessary.
Asked whether rescheduling might not help further research, Madras replied “The schedule is not the impediment to clinical trails.” The major obstacle to federal research, namely NIDA’s monopoly stranglehold on research supplies of marijuana, wasn’t mentioned by Madras and was touched on only tangentially by other witnesses.
Tile outside of the Federal Courtroom in Sacramento.
On day two of Dr. Madras’s cross examination, Gilg began by asking if cannabis met all the FDA criteria, would it still not be a medicine because it’s a plant? Madras replied, yes and because it’s psychoactive. Gilg then presented a 2005 study by Nicholas Downing reviewing 188 new drugs that were approved by the FDA. The median number of clinical trials performed on those drugs was two; 37% of the approved drugs had only one trial. When asked whether his surprised her, Madras replied, no because oftentimes the pharmaceutical company that develops drugs is the one that performs their trials.
Gilg asked Madras is she was aware of a recent study showing that adolescent marijauna use in Colorado is down. She said no she had not “excavated” that study, but claimed that in every state where medical marijuana is legal, marijuana use is up, according to NSDUH. Gilg then asked about a NSDUH study showing that the number of people diagnosed with substance abuse problems for marijuana had not changed between 2002 and 2012. Madras disputed it, and they went to the TED data, after which she finally confirmed the statement, but said Wilson Compton of NIDA has different figures. Madras also said that the new 2013 NSDUH data says 19 million people are using marijuana, 8 million of them daily, which she said represents an increase.
Gilg then explored studies showing that many of those in treatment for marijuana substance abuse are referred by the courts. Madras again resisted admitting this, and opined on this topic that this “may have been a public service” because 95% of people with substance abuse problems don’t seek treatment. She also tried to dodge around Gilg’s reading of a study showing that no marijuana users were placed in residential rehabilitation treatment, concluding this must mean it’s less dangerous than other drugs. Madras tried to say this could be for a variety of reasons, having to do with cost, insurance, and access to beds. “So people who smoke marijuana don’t have money or insurance?” Gilg asked. Madras conceded there also.
They then got into tolerance and withdrawal, with Madras claiming that “you can be hospitalized for pain drugs and not be an addict.” The new standard has to do with behavioral control and life consequences; parameters like time spent obtaining a drug, interpersonal problems, and using it after expressing a desire to stop. Gilg then brought out a chart rating caffeine on these addiction parameters, showing it was in many areas more troublesome than cannabis.
Dr. Madras’s brain imaging studies on cannabis users were then discussed, with Madras saying in her study and 42 others, cannabis causes dose-dependent changes in the brain, particularly in the hippocampus and medulla (two areas with a prevalence of CB1 receptors). She was made to admit, however, than longitudinal studies had not been done in this area. She also spoke about Nora Volkow’s study showing marijuana users had a “blunted response” to a dopamine agonist, similar to the response seen in cocaine and alcohol users. In her writings Madras said establishing causality “warrants caution,” and Gilg asked her why she wasn’t exercising caution in court. Studies on schizophrenia and driving were also discussed. Madras said she disagreed with a metaanalysis showing cannabis was only as harmful as penicillin when it comes to traffic fatalities, but Gilg listed three studies that concurred. Madras claimed that NHTSA studies conflicted, but those only show prevalence of use.
Largely unexplored in the hearings was the larger question as to whether FDA approval is a rational prerequisite for rescheduling in the first place. The original criterion spelled out in the Controlled Substances Act is “accepted medical use.” It was on this basis that DEA administrative law judge Francis Young ruled that cannabis clearly had medical use in his 1990 rescheduling decision. Subsequently, the DEA overruled Judge Young by promulgating a new regulation defining accept medical use to require controlled FDA studies. Whether the rationality of this criterion can be impugned through these court hearings is unclear.
Dr. Madras maintained a composed, thoughtful presence throughout her testimony, ably defending her contention that marijuana has not met the rigorous standards of FDA approval required of other pharmaceutical drugs. What remains to be seen is whether the court will find this a valid “rational basis” for keeping marijuana in Schedule One.
Judge Mueller gave the attorneys until Nov. 7 to do more briefing; a status conference is set for Nov. 19. Mueller’s ruling isn’t expected until December.