TO ALL MEMBERS OF THE NATIONAL INSTITUTE ON DRUG ABUSE'S NATIONAL
ADVISORY COUNCIL ON DRUG ABUSE
I had intended to submit information to the members of the National Advisory Council on Drug Abuse (NACDA) during the public comment period of the September 18, 2003, meeting, but a hurricane caused that meeting to be cancelled. I'm writing to you now to request that the NACDA issue two recommendations in order to facilitate FDA-approved scientific research with marijuana and MDMA (Ecstasy).
I'm requesting that
By way of introduction, I'm Rick Doblin, Ph.D., President of the Multidisciplinary Association for Psychedelic Studies (MAPS,www.maps.org), a non-profit research and educational organization. My Ph.D. is in Public Policy from Harvard's Kennedy School of Government, with my dissertation focusing on the regulation of the medical uses of Schedule I drugs. MAPS is working to sponsor scientific research investigating the safety and efficacy of the therapeutic uses of MDMA (Ecstasy) and marijuana, with the goal of developing them into FDA-approved prescription medicines. I estimate that it will cost roughly $5 million over 5 years to investigate thoroughly each clinical indication for marijuana or MDMA.
Requested Recommendation #1: NACDA Support for Privately-Funded Marijuana Production Facility
The US Supreme Court has recently let stand the Ninth Circuit Court of Appeals ruling that doctors can recommend marijuana to their patients without fear of having DEA revoke their licenses to prescribe scheduled drugs. As a result, additional state medical marijuana initiatives and legislative actions can be expected. In order to facilitate the resolution of the issue of the potential medical uses of marijuana through scientific research rather than just through the ballot box or legislative action, I'm requesting that NACDA support the establishment of a privately-funded facility to produce marijuana exclusively for use in federally-approved research.
The January 1998, NACDA document entitled, "The Provision of Marijuana and Other Compounds For Scientific Research," begins by noting that "Since its inception in 1974, NIDA has been the sole administrator of a contract to grow cannabis (marijuana) for research purposes and the only legal source for cannabis in the United States." For reasons explained below and in the enclosed letter sent to NIDA Director Nora Volkow on September 16, 2003, NIDA's monopoly stands squarely in the way of privately-funded research into the potential risks and benefits of the medical uses of marijuana.
As long as NIDA retains its monopoly on the supply of marijuana that can be used in research, private sponsors of medical marijuana research 1) cannot select the exact strain of marijuana with the exact mix of cannabinoid content that the sponsors consider most likely to be safe and efficacious, 2) cannot manufacture the drug they wish to research and thus are not in control of either availability and cost, and 3) cannot guarantee to supply the exact drug that was researched for possible prescription use since NIDA is legally authorized to grow marijuana for research but cannot supply it on a prescription basis. No rational sponsor will invest millions of dollars in medical marijuana research while it remains dependent for its supply of research material on NIDA, whose institutional mission is diametrically opposed to exploring the beneficial uses of marijuana and which cannot in any case legally provide marijuana for prescription use.
In order to facilitate a privately-funded, FDA-approved drug development research program, MAPS is currently seeking to sponsor a privately-funded marijuana production facility at UMass Amherst, under the direction of Prof. Lyle Craker, Director of the Laboratories for Natural Products, Medicinal and Aromatic Plants, Department of Plant and Soil Sciences. Dr. Craker initially submitted his application to DEA for a license to establish a growing facility on June 25, 2001. On July 24, 2003, after stonewalling for over two years, DEA finally posted the legally required Federal Register notice about Prof. Craker's application. The public comment period ended September 22, 2003 and a decision from the DEA is expected within the next month or two.
In "The Provision of Marijuana and Other Compounds For Scientific Research," the NACDA states that "Because of international treaty agreements (Single Convention on Narcotic Drugs, 1961) which prohibit entities other than the Federal Government from legally supplying cannabis, NIDA has remained its only legal source." Enclosed is a legal analysis of US obligations under the Single Convention, prepared by Peter Barton Hutt and Alexei Silverman, Covington & Burling (a prominent DC law firm), and Graham Boyd, ACLU Drug Policy Litigation Group. This analysis shows that the private production of marijuana is not prohibited by the Single Convention. Clear evidence supporting this analysis is the British Home Office's April 1998 licensing of the privately-funded GW Pharmaceuticals to grow marijuana for manufacture into marijuana extracts for medical research. The International Narcotic Control Board (INCB), which monitors compliance with the Single Convention, has not objected to the British Home Office licensing of GW Pharmaceuticals in any of its annual reports on treaty compliance.
Furthermore, U.S. laws that regulate the production of Schedule I drugs (21 C.F.R. 1301.33(b)) state that, "*In order to provide adequate competition,* the [DEA] Administrator shall *not* be required to limit the number of manufacturers in any basic class to a number less than that consistent with maintenance of effective controls against diversion *solely because* a smaller number is capable of producing an adequate and uninterrupted supply." [emphasis added] In other words, the laws governing the licensing of manufacturers of Schedule I drugs specifically address the possibility of monopolies and are written so that monopolies are not permitted to exist.
For your information, MAPS is working to address the concerns expressed in the Office of National Drug Control Policy (ONDCP)-funded Institute of Medicine (IOM) report on the medical uses of marijuana, which recommended the development of non-smoking delivery systems. MAPS and California NORML have funded laboratory research into the use of vaporizers that heat the marijuana but don't burn it, releasing a vapor stream that contains substantial amounts of cannabinoids without the products of combustion. Vaporizers are the only non-smoking delivery system that uses the marijuana plant itself rather than an extract. FDA is currently reviewing (and early indications are that it is likely to approve) the first human study to compare the subjective effects, cannabinoid blood levels, and amounts of expired carbon monoxide in subjects who both smoke marijuana and at a different time inhale the steam produced by vaporization (specifically from the Volcano vaporizer, www.vapormed.de). This clinical study will be conducted by Dr. Donald Abrams, UC San Francisco and will be funded by California's Center for Medicinal Cannabis Research. While we anticipate that there will be little functional differences between subjects either smoking or vaporizing high-potency marijuana, we propose to investigate this issue objectively by conducting clinical trials with both smoked and vaporized groups.
Requested Recommendation #2: NACDA Support for the Release of Information about NIDA-Funded MDMA (Ecstasy) Research Conducted by Dr. George Ricaurte and Dr. Una McCann
In early September 2003, Drs. Ricaurte and McCann retracted an article they published a year before in Science in which they reported that what they considered a common recreational dose regimen of MDMA caused severe dopaminergic neurotoxicity that could lead to Ecstasy users developing Parkinson's. The research was retracted since it turned out that all but one of the primates used for the research published in Science were mistakenly administered methamphetamine instead of MDMA. The mistake was claimed to have resulted from the mislabeling by the supplier, Research Triangle Institute (RTI), of two10 gram bottles of MDMA and methamphetamine, delivered by RTI to Drs. Ricaurte and McCann in the same shipment.
In a September 18, 2003, letter to NIDA Director Dr. Nora Volkow (enclosed) and in a Freedom of Information Act (FOIA)-request, MAPS asked NIDA to release specific additional information about some of the NIDA-funded research conducted by Drs. Ricaurte and McCann. I'm now asking that the NACDA recommend the release of the information specified in the letter and in the FOIA request. That information includes 1) A list of all the studies that were conducted with mislabeled MDMA or methamphetamine, including the amounts of mislabeled MDMA or methamphetamine used in each study, the route of administration, the number and type of animal, the death rate of those animals, the starting and concluding dates of those studies, and whether the studies in question need to be retracted or have yet to be published, and 2) The doses, routes of administration (oral or injection), number and kind of animals, ambient temperatures, and starting and concluding dates for all the failed attempts with genuine MDMA to replicate the erroneous findings reported in the now-retracted Science article.
A September 18, 2003 editorial in Nature, which is enclosed, calls on NIDA Director Nora Volkow to conduct a "thorough public review of the circumstances and participant's roles in one of the more bizzare episodes in the history of drug research." A September 18, 2003 article in The Scientist, also enclosed, mentions a second article that was retracted by Drs. Ricaurte and McCann and reports that two senior British scientists have written to the editor of Science requesting that Science conduct an independent inquiry and release the peer-reviewers comments on the original article.
Unfortunately, the retraction letter leaves quite a few questions unanswered. Drs. Ricaurte and McCann report having used in various research studies the entire 10 grams of what they thought was MDMA before they later learned that the bottle actually contained methamphetamine. At this point in time, only two papers have been retracted, in which no more than 2 1/4 grams of material was administered to the test animals. At least 7 3/4 grams of mislabeled methamphetamine used in research studies remains unaccounted for. In addition, there has been no accounting of which studies used any of the 10 grams of what was considered to be methamphetamine but was later determined to be MDMA.
In the retraction letter, Drs. Ricaurte and McCann still claim that doses of MDMA used by some humans could cause dopaminergic neurotoxicity. The retraction letter concludes by stating that, "it remains possible that dose regimens in the range of those used by some humans, but different from those thus far tested, produce dopamine neurotoxicity in primates, as they do in rodents. Moreover, lasting effects of MDMA on dopaminergic function in humans have recently been reported, and some humans with a history of MDMA abuse have developed Parkinsonism. However, until the dopamine neurotoxic potential of MDMA in primates can be examined more fully, this possibility remains uncertain." Since MAPS is seeking to conduct FDA-approved research in which MDMA is administered to human subjects, we are requesting the release of more details about the results of Dr. Ricaurte and McCann's subsequent studies administering genuine MDMA to primates in which they found no evidence of dopaminergic neurotoxicity. These studies provide data that bears directly on the estimation of the risk of dopaminergic neurotoxicity to subjects in the human research that MAPS is seeking to conduct.
For your information, MAPS has both FDA and IRB approval for a double-blind, placebo-controlled pilot study investigating the use of MDMA-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder (PTSD). This pilot study will be the first FDA-approved investigation of the therapeutic use of MDMA ever conducted. The study can begin once Dr. Michael Mithoefer receives a Schedule I license from the Drug Enforcement Administration (DEA). Dr. Mithoefer applied over 15 months ago to the DEA for his license to handle a total of 3 grams of MDMA that will be administered to the subjects in his study (protocol and related information posted at http://www.maps.org/mdma/). DEA has scheduled an inspection of Dr. Mithoefer's facility for October 28 and we anticipate that he will probably receive his Schedule I license shortly thereafter.
Though a separate issue, it's important to note that the massive serotonin reductions in Ecstasy users that Drs. McCann and Ricaurte reported in their 1998 Lancet PET paper have not been replicated by Buchert et al.'s much larger (N=117 v. N=29) and better controlled PET study published in 2003 in the Journal of Nuclear Medicine. Images from the Lancet paper that are now generally considered methodologically flawed were used by NIDA in its major anti-ecstasy campaign, which has been withdrawn.
I look forward to learning what recommendations, if any, the NACDA decides to make concerning the production of marijuana for federally-approved research and the release of additional information about Drs. Ricaurte and McCann's NIDA-funded MDMA and methamphetamine research. The controversy over the medical use of marijuana deserves to be resolved through FDA-approved scientific research, which NACDA can facilitate by supporting the establishment of a privately-funded production facility. Regarding Drs. Ricaurte and McCann's research with mislabeled MDMA and methamphetamine, NACDA can help strengthen NIDA's credibility, which is its most essential asset, especially in regards to the drug abuse prevention and educational campaigns that it conducts, by recommending that additional informed be released.
If you need any additional information, I can be reached at 617 484-8711.
Rick Doblin, Ph.D.
MAPS Sept. 16, 2003 letter to NIDA Director Dr. Nora Volkow
Covington & Burling/ACLU legal analysis of US Int. treaty obligations
MAPS Sept. 18, 2003 letter to NIDA Director Dr. Nora Volkow
September 18, 2003 editorial in Nature
September 18, 2003 article in The Scientist