House of Commons - Science and Technology

Select Committee on Science and Technology Written Evidence

APPENDIX 7

Memorandum from the Multidisciplinary Association for Psychedelic Studies (MAPS)

1. This submission comes from the Multidisciplinary Association for Psychedelic Studies (MAPS), a United States nonprofit organization whose mission is to develop Schedule I substances that may have medical or psychotherapeutic benefits into prescription medicines. This mission has made us familiar with the process in the United States for gathering scientific evidence relating to the classification of illegal drugs, and the ways that this evidence is and is not incorporated into public policy decisions. We write to share our knowledge of this process and both its functional and nonfunctional elements, so that your committee might become aware of potential pitfalls that may also exist in England.

2. In the United States, the process for gaining the necessary permissions to conduct scientific research using currently prohibited substances is different for cannabis than for other Schedule I substances such as MDMA, LSD, or psilocybin. Despite broad interest among United States citizens and State governments, the process for conducting research into the medical uses of cannabis is seriously obstructed. This submission will first share information about the research requirements for substances other than cannabis, followed by a description of MAPS' experience with the politically hobbled process for getting cannabis approved as a prescription medicine.

3. MAPS has sponsored and assisted researchers in gaining approval to proceed with several studies involving MDMA (Ecstasy), and psilocybin. Currently, a study is underway in South Carolina investigating the use of MDMA to facilitate psychotherapy in patients with posttraumatic stress disorder (PTSD), with promising results. Similar MAPS-sponsored studies using MDMA-assisted psychotherapy to treat PTSD are fully-approved in Israel and under review in Switzerland. A study at Harvard Medical School testing MDMA to ease anxiety associated with advanced-stage cancer has received final approved from the DEA on 19 January 2006 and will begin soon. A completed pilot study at the University of Arizona-Tucson found positive benefits from the effects of psilocybin in reducing symptoms of obsessive-compulsive disorder (OCD).

4. The process for conducting studies with substances other than cannabis has mostly worked well, with some room for improvement. In order to proceed with research, the researcher must have the protocol approved by the Food and Drug Administration (FDA) and a non-governmental Institutional Review Board (IRB-also known as ethics committees), must obtain a Schedule I license from the Drug Enforcement Administration (DEA) and the appropriate State agency, and must obtain a legal source for the drugs to be studied. The FDA has for the last 16 years, as a matter of policy, reviewed psychedelic and medical marijuana protocols based on their scientific merit and not on political factors. Many IRBs also prioritize science. The DEA has by law a limited set of criteria that it can use to justify denying a Schedule I licence. This allows researchers to know in advance the likelihood of being able to obtain the license, encouraging the design of protocols involving Schedule I substances, and investment in research planning. One potential challenge is that while the FDA must review a research protocol within 30 days, the DEA has no time limit for responding to applications for a Schedule I licence. As will be apparent in our discussion of the process with cannabis research, this loophole potentially allows the DEA to obstruct research by indefinitely delaying responding to licence applications. To date, the DEA has taken substantially more than 30 days for the non-cannabis studies with which MAPS has been involved but in the end has approved the licenses, though sometimes only after inquiries from elected representatives. State agencies have issued Schedule I licences in a more timely manner. Most importantly, in terms of research materials, except for marijuana, there is a competitive market for the supply of all Schedule I substances, which are obtained from independent suppliers licensed by the DEA.

5. Unfortunately, the process for conducting medical cannabis research, despite its broad support by the public and the medical community, serves as an example for England of what not to do in designing the process of incorporating scientific knowledge into public policy decisions. Ideally, if the FDA determines that the use of the cannabis plant is safe and efficacious for some clinical indication, a physicians should be able to prescribe it in the form of an FDA-approved medicine that is standardized for purity and potency. For this outcome to be realized, a pharmaceutical company must first submit to FDA sufficient scientific data proving safety and efficacy in a specific patient population, with the data gathered in controlled clinical trials conducted with prior approval of the FDA and DEA.[11]

6. Despite persisting interest in the medical research community into the exploration of the medical uses of cannabis, no patients in the United States received cannabis in the context of an FDA-approved study during the 14-year period between 1984 and 1998, when Dr Donald Abrams at the University of California—San Francisco administered smoked cannabis to the first HIV+ subject in his groundbreaking study.[12] Dr Abrams struggled for five years to obtain permission to conduct a MAPS-sponsored study of marijuana in subjects with AIDS-wasting, three years of which was involved with a fruitless effort to obtain cannabis from the National Institute on Drug Abuse (NIDA) after his initial protocol had been approved by FDA.[13] Following and precipitated by California's 1996 passage of Proposition 215, which provided legal access to cannabis for patients whose physicians recommended it to them, the National Institute on Drug Abuse (NIDA) agreed to sponsor a redesigned version of Dr Abrams' study, contingent upon a new focus on safety in HIV+ subjects without AIDS wasting.

Federal agencies have blocked the supply of cannabis for clinical research through unreasonable delay of applications.

7. The most serious barrier to medical marijuana research in the US has been DEA's and NIDA's obstruction of FDA-approved studies' ability to obtain a supply of cannabis for their research. MAPS' experience attempting to support medical cannabis research illustrates the importance of having adequate competition in the market for the research material, and also of divorcing the supply process from government agencies that have a conflict of interest that prevents objective research.

8. In the United States, NIDA has a monopoly on the supply of FDA-approved research-grade cannabis for use in human subjects.[14] Sponsors of research into the medical uses of cannabis cannot manufacture their own supplies but must instead petition to purchase federal supplies at cost from NIDA.[15] The NIDA monopoly has been an impediment to objective and accurate scientific research. NIDA's institutional mission is to sponsor research into the understanding and treatment of the harmful consequences of the use of illegal drugs and to conduct educational activities to reduce the demand for and use of these illegal drugs.[16] NIDA's mission makes it a singularly inappropriate agency to be responsible for expeditiously stewarding scientific research into potential beneficial medical uses of cannabis. Furthermore, as with many monopolies, the quality of its product is low,[17] and access is restricted.

9. Accordingly, members of the medical community have opposed NIDA's policies relating to the supply of cannabis for scientific research into its potential medical uses. In December 1997, the American Medical Association (AMA) House of Delegates urged the National Institutes of Health (NIH) to facilitate "well-designed clinical research into the medical utility of marijuana."[18] The Delegates stressed that "marijuana of various and consistent strengths and/or placebo" should be supplied by NIDA to clinical researchers who have received FDA approval, "regardless of whether or not the NIH is the primary source of grant support".[19] However, NIDA has resisted supplying research cannabis to MAPS' privately funded studies, which has limited research and hobbled the process by which cannabis could become available as a prescription medicine. This has not been the case in the United Kingdom, where GW Pharmaceuticals has been able to grow cannabis for extracts for use in clinical trials.

10. Cannabis research is further complicated by the fact that NIH's Department of Health and Human Services created guidelines and requirements that only apply to cannabis research, and that depart from the process for research using any other proposed medicine—not facilitating research as the AMA suggested, but doing just the opposite. HHS's guidelines require sponsors of privately funded and FDA-approved protocols who seek to purchase supplies from NIDA to submit their protocols for review and approval to the Public Health Service (PHS), an additional review process that exists exclusively for cannabis research.[20] HHS guidelines also specified a limited number of medical conditions for which cannabis should be tested, suggested that researchers conduct only "multi-patient" studies rather than the "single-patient" studies that FDA also considers scientifically valid, and discouraged researchers from conducting studies with the goal of getting natural cannabis approved as a prescription medicine. In addition, although FDA's statutory requirement is to approve a drug if it is proven safe and efficacious as compared to placebo (since some patients may respond best to a medicine that is not on average equal to or better than other medicines), HHS guidelines recommended that protocols be designed to prove cannabis equal or superior to existing medications.[21] None of these restrictions apply to research with any other substance, even those in Schedule I. Especially problematic, the HHS guidelines established no time limits within which HHS must evaluate protocols submitted to it for review, and the supposed peer-reviews are conducted entirely by government employees without any established appeal process.

11. Almost immediately, HHS's policy had a chilling effect on medical cannabis research. In September 1999, Dr Ethan Russo received FDA approval for a protocol designed to examine the medical uses of cannabis in treatment-resistant migraine patients.[22] In February 2000, NIDA refused to supply Dr Russo with cannabis, based on criticisms of the protocol design by the PHS reviewers.[23] Since Dr Russo's protocol was approved by FDA and would have been privately funded, the decision by PHS and NIDA not to provide the cannabis at cost effectively halted the standard FDA drug development process.

Dr Lyle Craker's request for a licence to operate a cannabis production facility at UMass Amherst

12. To help remedy the supply problem, Prof Lyle Craker, the Director of the Medicinal Plant Program of the Department of Plant and Soil Sciences at the University of Massachusetts—Amherst, with sponsorship from MAPS, applied in June 2001 to DEA for a licence to establish a small medical cannabis production facility to supply high-quality research material to researchers with FDA and DEA-approved protocols.[24] Over four and a half years later, Prof Craker is in the midst of DEA Administrative Law Judge hearings and remains stuck in a bureaucratic morass.

13. A chronology of Prof Craker's application illustrates the inadequate and obstructed process for furthering medical cannabis research. In December 2001, Prof Craker was told by DEA that his application was lost. In February 2002, DEA refused to accept a photocopy of the application since it lacked an original signature, despite DEA having claimed to have lost the original document. On 6 June 2002, five Massachusetts Congressional Representatives sent a letter to DEA Administrator Asa Hutchinson expressing support for the licensing of a privately-funded cannabis production facility.[25] On 1 July 2002, Administrator Hutchinson replied to the Congressmen, stating DEA opposition to private production facilities based on supposed restrictions imposed by US international treaty obligations.[26] Later in July 2002, DEA returned the original application to Prof Craker, unprocessed, with no individual's name on the return address or cover note, and with a DEA date-stamp showing that it had, in fact, been received by DEA in June 2001. In August 2002, Prof Craker resubmitted his original application, along with an analysis of US international treaty obligations demonstrating that private production facilities were not prohibited.[27] On 16 December 2002, two DEA agents traveled to UMass Amherst to meet with Prof Craker and senior UMass Amherst officials. The DEA agents encouraged them to withdraw the application, which they declined to do.

14. On 4 March 2003, more than 20 months after his original application was filed, Prof Craker received his first written reply from DEA, indicating that he would need to submit "credible evidence" supporting his assertion that researchers were not adequately served by NIDA cannabis.[28] Prof Craker responded to this request on 2 June 2003. In October, 2003, DEA again heard from elected representatives in support of Prof Craker's application, when Massachusetts Senators Edward Kennedy and John Kerry sent a letter stating their opposition to the NIDA monopoly on research cannabis. The Senators noted that lack of adequate competition "jeopardizes important research into the therapeutic effects of marijuana for patients undergoing chemotherapy or suffering from AIDS, glaucoma, or other diseases."[29]

15. In addition to the delay tactics cited above, DEA has blatantly failed to follow the notice procedures and due process mandated by law regarding applications such as that submitted by Prof Craker. In July 2004, Prof Craker and MAPS sued DEA in the Court of Appeals for the District of Columbia for unreasonable delay in responding to Prof Craker's application. The DC Court of Appeals issued a decision in November 2004, ordering DEA to reply to the Court with its reasons for the delay.[30] Rather than reply to the court's order, DEA instead finally rejected Dr Craker's application,[31] which he is now challenging through the DEA Administrative Law Judge hearing process. The hearings began in August 2005[32] and the Administrative Law Judge should issue a recommendation around June 2006.

Chemic Laboratories' request to obtain 10 grams of cannabis for a non-clinical study

16. The government also delayed and ultimately rejected the application of Chemic Laboratories, of Canton, Massachusetts ("Chemic") to obtain marijuana for a MAPS-sponsored study to evaluate the contents of the vapor stream from a cannabis vaporizer, that heats marijuana without burning it.[33] This study neither involves human subjects nor requires FDA approval, but would provide valuable knowledge about alternative cannabis delivery systems that might spare patients exposure to the potentially harmful elements of cannabis smoke.

17. On June 24, 2003, Chemic submitted separate but related applications to the US Department of Health and Human Services (HHS) and DEA seeking, respectively, approval of its research protocol so that Chemic could purchase 10 grams of cannabis from NIDA, and registration to import 10 grams of cannabis from the Dutch Office of Medical Cannabis ("DOMC"), part of the Dutch Ministry of Health. The DOMC operates in compliance with all international treaty obligations and is authorized to export cannabis to fully-licensed research projects. DOMC can supply cannabis of a quality that is unavailable from NIDA and that is required to complete the later phase of the vaporizer study. DEA verbally advised Chemic that it would not process the application until HHS determined the scientific merit of the vaporizer protocol. DEA also failed to publish a notice in the Federal Register, as is required by statute "upon the filing" of an import application.[34]

18. HHS failed to decide upon the scientific merit of the research protocol for over two years. HHS' first communication to Chemic with respect to its application came on October 10, 2003, more than three months after it was submitted, stating that there was insufficient information in the application to judge the merits of the protocol. Although the application had complied fully with HHS' announced procedures, Chemic submitted an expanded and revised protocol on January 29, 2004. In the months after this submission, Chemic made repeated attempts to ascertain the status of its application, which HHS officials refused to divulge. A communication from HHS indicated that the application was stalled awaiting the PHS review required only for cannabis research.[35]

19. On June 9, 2004, MAPS received a letter from NIDA that is perhaps the most telling evidence of the futility of pursuing medical cannabis research under the current regulatory system. In this letter, NIDA Director Dr. Nora Volkow explained that

These statements highlight NIDA's conflict of interests, and the resulting chilling effect that the NIDA monopoly has on research that could demonstrate how medical cannabis can help sick patients.

20. On July 14, 2004, MAPS and Valerie Corral[37] filed a lawsuit in the Court of Appeals for the District of Columbia against both HHS and DEA, alleging unreasonable delay in processing these applications. Unfortunately, the Court ruled on November 22, 2004 that HHS' delay had not been so unreasonable as to justify mandamus and dismissed the lawsuit without prejudice,[38] HHS waited another nine months before rejecting Chemic's protocol and recommending that NIDA deny Chemic the 10 grams,[39] thus blocking this avenue of research. Chemic has appealed and addressed each of the HHS critiques, but five months later has heard nothing.

21. Fortunately, the lack of an independent source of cannabis for use in FDA-approved clinical trials is an aberration and not the norm for Schedule I drugs. However, this aberration is a formidable obstacle to pursuing medical marijuana research and creating a marijuana policy that is based on current science. In our opinion, the features of this policy that most obstruct research are twofold. First, the existence of a monopoly on research supply reduces product quality and access below the level at which good scientific research can flourish. Second, government agencies designed to control drug abuse have an institutional mission that will inherently bias them against investigations into the beneficial uses of Schedule I drugs. The DEA's and NIDA's recalcitrance against allowing even non-clinical trials that may forward the cause of prescription cannabis demonstrates the importance of leaving decisions effecting research in the hands of government agencies (such as the equivalent of our FDA) that will prioritize science over politics. We hope that in England your government designs a policy that facilitates research and supports informed policymaking.

January 2006

(1 February 2000),available at http://www.maps.org/mmj/russo1199/02010001.html

11 See Food and Drug Administration, Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (1998), available at http://www.fda.gov/cder/guidance/1397fnl.pdf Back

12 Donald Abrams, Medical Cannabis:Tribulations and Trials. 30 Journal of Psychoactive Drugs, Apr-Jun 1998), at 163-69. Back

13 Id. Back

14 NIDA contracts with the University of Mississippi to grow cannabis for research purposes, under the direction of Professor Mahmoud ElSohly. The University of Mississippi facility holds the only licence issued by the DEA for the production of cannabis for human consumption. Back

15 FDA has not permitted researchers to use seized cannabis for research purposes due to uncertain purity and the inability to conduct subsequent studies with a standardized and replicable product. Back

16 See website of the National Institute on Drug Abuse, http://www.drugabuse.gov/about/AboutNIDA.html Back

17 MAPS and California NORML conducted a scientific study of the potency of cannabis used by patients across the country. This potency was then compared to the average potency of the cannabis that NIDA provides to the seven remaining patients who are part of the Compassionate Investigational New Drug program. Patients preferred cannabis that was roughly three to four times more potent than what NIDA supplies. The primary advantage of more potent cannabis is that it enables patients to inhale less smoke and particulate matter per unit of therapeutic cannabinoids. Dale Gieringer, Ph.D. Medical Cannabis Potency Testing Project, 9 MAPS, Autumn 1999, available at http://www.maps.org/news-letters/v09n3/09320gie.html, at 20-22. Back

18 Council on Scientific Affairs, AMA House of Delegates, Report 10-Medical Marijuana, Recommendations (1997). Back

19 Id. Back

20 The new HHS guidelines read, "After submission, the scientific merits of each protocol will be evaluated through a Public Health Service interdisciplinary process." Id. Back