04-7218. Schedules of Controlled Substances: Placement of alpha-methyltryptamine and 5-methoxy-N,N-diisopropyltryptamine Into Schedule I of the Controlled Substances Act

AGENCY:

Drug Enforcement Administration (DEA), Department of Justice.

ACTION:

Notice of proposed rulemaking.

SUMMARY:

The Acting Deputy Administrator of the Drug Enforcement Administration (DEA) is issuing this notice of proposed rulemaking to place alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) into Schedule I of the Controlled Substances Act (CSA). This proposed action is based on data gathered and reviewed by the DEA. If finalized, this proposed action would continue to impose the criminal sanctions and regulatory controls of Schedule I substances under the CSA on the manufacture, distribution, and possession of AMT and 5-MeO-DIPT.

DATES:

Written comments must be postmarked, and electronic comments must be sent, on or before April 30, 2004.

ADDRESSES:

To ensure proper handling of comments, please reference “Docket No. DEA-252” on all written and electronic correspondence. Written comments being sent via regular mail should be sent to the Acting Deputy Administrator, Office of Diversion Control, Drug Enforcement Administration, Washington, DC 20537, Attention: DEA Federal Register Representative/CCD. Written comments sent via express mail should be sent to DEA Headquarters, Attention: DEA Federal Register Representative/CCD, 2401 Jefferson-Davis Highway, Alexandria, VA 22301. Comments may be directly sent to DEA electronically by sending an electronic message to [e-mail]. Comments may also be sent electronically through http://www.regulations.gov using the electronic comment form provided on that site. An electronic copy of this document is also available at the http://www.regulations.gov Web site. DEA will accept electronic comments containing MS word, WordPerfect, Adobe PDF, or Excel files only. DEA will not accept any file format other than those specifically listed here.

FOR FURTHER INFORMATION CONTACT:

Christine Sannerud, Ph.D., Chief, Drug and Chemical Evaluation Section, Drug Enforcement Administration, Washington, DC 20537, [phone].

SUPPLEMENTARY INFORMATION:

On April 4, 2003, the Deputy Administrator of the DEA published a final rule in the Federal Register amending § 1308.11(g) of title 21 of the Code of Federal Regulations to temporarily place AMT and 5-MeO-DIPT (68 FR 16427) into Schedule I of the CSA pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). This final rule, which became effective on the date of publication, was based on findings by the Deputy Administrator that the temporary scheduling of AMT and 5-MeO-DIPT was necessary to avoid an imminent hazard to the public safety. The CSA (21 U.S.C. 811(h)(2)) requires that the temporary scheduling of a substance expire at the end of one year from the date of issuance of the order. However, if proceedings to schedule a substance pursuant to 21 U.S.C. 811(a)(1) are pending, the temporary scheduling of a substance may be extended for up to six months. Under this provision, the temporary scheduling of AMT and 5-MeO-DIPT, which would expire on April 3, 2004, may be extended to October 3, 2004. This extension is being ordered by the DEA Acting Deputy Administrator in a separate action.

In accordance with 21 U.S.C. 811(b) of the CSA, DEA has gathered and reviewed the available information regarding the pharmacology, chemistry, trafficking, actual abuse, pattern of abuse, and the relative potential for abuse of AMT and 5-MeO-DIPT. The Acting Deputy Administrator has submitted these data to the Acting Assistant Secretary for Health, Department of Health and Human Services. In accordance with 21 U.S.C. 811(b), the Acting Deputy Administrator also requested a scientific and medical evaluation and a scheduling recommendation for AMT and 5-MeO-DIPT from the Acting Assistant Secretary for Health. The Food and Drug Administration (FDA) has notified the DEA that there are no exemptions or approvals in effect under 21 U.S.C. 355 of the Food, Drug and Cosmetic Act for AMT and 5-MeO-DIPT. A search of the scientific and medical literature revealed no indications of current medical use of AMT and 5-MeO-DIPT in the United States.

Explanation of Alpha-methyltryptamine and 5-methoxy-N, N-diisopropyltryptamine

Alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) are tryptamine (indoleethylamine) derivatives and share several similarities with the Schedule I tryptamine hallucinogens such as alpha-ethyltryptamine (AET) and N,N-dimethyltryptamine (DMT). Several other tryptamines also produce hallucinogenic/stimulant effects and are controlled as Schedule I substances under the CSA (bufotenine, diethyltryptamine, psilocybin and psilocyn). Although tryptamine itself appears to lack consistent hallucinogenic/stimulant effects, substitutions on the indole ring and the ethylamine side-chain of this molecule result in pharmacologically active substances (McKenna and Towers, J. Psychoactive Drugs, 16: 347-358, 1984). The chemical structures of AMT and 5-MeO-DIPT possess the critical features necessary for hallucinogenic/stimulant activity. In drug discrimination studies, both AMT and 5-MeO-DIPT substitute for 1-(2,5-dimethoxy-4-methylphenyl)-aminopropane (DOM), a phenethylamine-based hallucinogen in Schedule I of the CSA. The potencies of DOM-like discriminative stimulus effects of these and several other similar tryptamine derivatives correlate well with their hallucinogenic potencies in humans (Glennon et al., Eur. J. Pharmacol. 86: 453-459, 1983).

AMT, besides its full generalization to DOM, also partially mimics amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in drug discrimination tests in experimental animals. AMT increases systolic and diastolic arterial blood pressures, dilates pupils and produces strong motor stimulant effects. The behavioral effects of orally administered AMT (20 mg) in humans are slow in onset, occurring after 3 to 4 hours, and gradually subsiding after 12 to 24 hours, but may last up to 2 days in some subjects. The majority of the subjects report euphoria, stimulation, muscle tension, muscle ache, nervous tension, irritability, restlessness, dizziness, impaired motor coordination, unsettled feeling in stomach, inability to relax and sleep, and visual effects such as blurry vision, apparent movement of objects, sharper outlines, brighter colors, longer after images, and visual hallucinations. The majority of the subjects equate the effects of a 20 mg dose of AMT to those of 50 micrograms of lysergic acid diethylamide (LSD). AMT also produces dextroamphetamine-like mood elevating effects in humans (Hollister et al., J. Nervous Ment. Dis., 131: 428-434, 1960; Murphree et al., Clin. Pharmacol. Ther. 2: 722-726, 1961).

Similar to other classical hallucinogens, AMT binds to serotonin receptors. It also inhibits 5-HT uptake, induces catecholamine release and inhibits monoamine oxidase activity. The available experimental evidence suggests that both serotonergic and dopaminergic systems mediate behavioral effects of AMT.

5-MeO-DIPT produces pharmacological effects similar to those of several Schedule I hallucinogens. The synthesis and preliminary human psychopharmacology study on 5-MeO-DIPT was first published in 1981 (Shulgin and Carter, Comm. Psychopharmacol. 4: 363-369, 1981). According to this report, subjective effects of 5-MeO-DIPT are substantially similar to those of MDMA, 3,4-methylenedioxyamphetamine (MDA) and 4-Bromo-2,5-dimethoxyphenethylamine (2C-B). 5-MeO-DIPT is an orally active hallucinogen. Following oral administration of 6-10 mg, 5-MeO-DIPT produces subjective effects with an onset of about 20-30 minutes, a peak at about 1-1.5 hours and duration of about 3-6 hours. Subjects who have been administered 5-MeO-DIPT are talkative and disinhibited. 5-MeO-DIPT dilates pupils. High doses of 5-MeO-DIPT produce nausea, jaw clenching, muscle tension and overt hallucinations with both auditory and visual distortions. As mentioned above, 5-MeO-DIPT fully mimics the discriminative stimulus effects of DOM, a Schedule I hallucinogen. According to the discriminative stimulus studies conducted by the Drug Evaluation Committee of the College on Problems of Drug Dependence, 5-MeO-DIPT dose-dependently (0.1-3 mg/kg, IP) generalizes to LSD with a maximal response of about 70% at doses (3 mg/kg) that severely disrupted responding.

Control of AMT and 5-MeO-DIPT

The abuse of stimulant/hallucinogenic substances in popular all night dance parties (raves) and in other venues has been a major problem in Europe since the 1990s. In the past several years, this activity has spread to the United States. The Schedule I controlled substance MDMA and its analogues, collectively known as Ecstasy, are the most popular drugs abused at these raves. Their abuse has been associated with both acute and long-term public health and safety problems. These raves have also become venues for the trafficking and abuse of other substances in place of or in addition to “Ecstasy.” AMT and 5-MeO-DIPT belong to such a group of substances.

The abuse of AMT and 5-MeO-DIPT began to spread in 1999. Since that time, these tryptamines have been encountered by law enforcement agencies in several states. These substances have been commonly encountered in tablet, capsule or powder forms. The tablet form often bears imprints commonly seen on MDMA tablets such as spider, alien head and “?” logos. These tablets also vary in colors such as pink, purple, red, and orange. The powder in capsule was also found to vary in colors such as white, off-white, gray, and burnt orange. Data from law enforcement officials indicate that 5-MeO-DIPT is often sold as “Foxy” or “Foxy Methoxy”, while AMT has been sold as “Spirals” at least in one case. Data gathered from published studies indicate that these are administered orally at doses ranging from 15-40 mg for AMT and 6-20 mg for 5-MeO-DIPT.

According to the Florida Department of Law Enforcement (FDLE), the abuse by teens and young adults of AMT and 5-MeO-DIPT is an emerging problem. There have been reports of abuse of AMT and 5-MeO-DIPT at clubs and raves in Arizona, California, Florida, and New York. Many tryptamine-based substances are illicitly available from United States and foreign chemical companies and from individuals through the Internet. There is also evidence of attempted clandestine production of AMT and 5-MeO-DIPT in Nevada, Virginia, and Washington, DC.

According to the data from System to Retrieve Information on Drug Evidence (STRIDE), Federal law enforcement authorities seized 31 drug exhibits and filed 13 cases pertaining to the trafficking, distribution and abuse of AMT during 1999 to 2003. The corresponding STRIDE data for 5-MeO-DIPT included 59 drug exhibits pertaining to 28 cases. AMT drug seizures included 21 capsules and 1,006 grams of powder, while 5-MeO-DIPT drug seizures included 11,373 tablets, 560 capsules, and 6,531.6 grams of powder. From 2001 to 2003, National Forensic Laboratory Information System (NFLIS) registered 10 and 12 cases of AMT and 5-MeO-DIPT, respectively. AMT drug exhibits included 17 dosage units and 7.53 grams of powder, while 5-MeO-DIPT drug exhibits included 24 capsules, 3 tablets and 14.42 grams of powder. In addition, there have been several local cases involving trafficking and abuse of AMT and 5-MeO-DIPT.

AMT and 5-MeO-DIPT share substantial chemical and pharmacological similarities with other Schedule I tryptamine-based hallucinogens in Schedule I of the CSA. AMT shares pharmacological effects of amphetamine, a stimulant, and DOM and LSD, the Schedule I hallucinogens. AMT acts as a stimulant, produces euphoria and increases heart rate and blood pressure. The evidence suggests that 5-MeO-DIPT mimics pharmacological effects of MDMA, MDA, and 2C-B, the Schedule I hallucinogens. It also partially mimics amphetamine effects. The risks to the public health associated with the above mentioned controlled substances are well known and documented. AMT and 5-MeO-DIPT, similar to other tryptamine-or phenethylamine-based hallucinogens, through the alteration of sensory perception and judgment can pose serious health risks to the user and the general public. Tryptamine, the parent molecule of AMT and 5-MeO-DIPT, is known to produce convulsions and death in animals (Tedeschi et al., J. Pharmacol. Exp. Ther. 126: 223-232, 1959). Following extensive studies on AMT as a possible antidepressant drug in 1960s, the Upjohn Company concluded that AMT is a highly toxic substance and discontinued the clinical studies on this substance. In fact, there were two recent published case reports describing the instances of emergency department admissions resulting from abuse of AMT and 5-MeO-DIPT in 2003 (Long et al., Vet. Human Toxicol., 45: 149, 2003; Meatherall and Sharma, J. Anal. Toxicol., 27: 313-317, 2003). There has been at least one confirmed death caused by the abuse of AMT in Florida in 2003. The above data show that the continued, uncontrolled tablet or capsule production, distribution and abuse of AMT and 5-MeO-DIPT pose hazards to the public health and safety. There are no recognized therapeutic uses of these substances in the United States.

The Acting Deputy Administrator, based on the information gathered and reviewed by her staff and after consideration of the factors in 21 U.S.C. 811(c), believes that sufficient data exist to support the placement of AMT and 5-MeO-DIPT into Schedule I of the CSA pursuant to 21 U.S.C. 811(a). The specific findings required pursuant to 21 U.S.C. 811 and 812 for a substance to be placed into Schedule I are as follows:

(1) The drug or other substance has a high potential for abuse.

(2) The drug or other substance has no currently accepted medical use in treatment in the United States.

(3) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Before issuing a final rule in this matter, the DEA Acting Deputy Administrator will take into consideration the scientific and medical evaluation and scheduling recommendation of the Department of Health and Human Services in accordance with 21 U.S.C. 811(b). The Acting Deputy Administrator will also consider relevant comments from other concerned parties.

Interested persons are invited to submit their comments, objections, or requests for a hearing in writing, with regard to this proposal. Requests for a hearing should state with particularity the issues concerning which the person desires to be heard. All correspondence regarding this matter should be sent to the Drug Enforcement Administration according to the instructions found in the Addresses section of this proposed rule. In the event that comments, objections or requests for a hearing raise one or more questions that the Acting Deputy Administrator finds warrants a hearing, the Acting Deputy Administrator shall publish a hearing notice in the Federal Register summarizing the issues to be heard and setting the time for the hearing.

Regulatory Certifications

Regulatory Flexibility Act

The Acting Deputy Administrator hereby certifies that this proposed rule has been drafted in accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)), has reviewed this regulation, and by approving it certifies that this regulation will not have a significant economic impact on a substantial number of small entities. This proposed rule, if promulgated, would permanently place AMT and 5-MeO-DIPT into Schedule I of the Controlled Substances Act.

Executive Order 12866

This proposed rule is not a significant regulatory action for the purposes of Executive Order (E.O.) 12866 of September 30, 1993. Drug scheduling matters are not subject to review by the Office of Management and Budget (OMB) pursuant to provisions of E.O. 12866, § 3(d) (1).

Executive Order 12988

This regulation meets the applicable standards set forth in sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice Reform.

Executive Order 13132 Federalism

This proposed rulemaking will not have substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government. Therefore, in accordance with Executive Order 13132, it is determined that this proposed rulemaking will not have sufficient federalism implications to warrant the preparation of a federalism assessment.

Unfunded Mandates Reform Act

This proposed rulemaking will not result in the expenditure by State, local and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more in any one year, and it will not significantly or uniquely affect small governments. Therefore, no actions were deemed necessary under provisions of the Unfunded Mandates Reform Act of 1995.

Small Business Regulatory Enforcement Fairness Act of 1996

This proposed rulemaking is not a major rule as defined by § 804 of the Small Business Regulatory Enforcement Fairness Act of 1996. This rule will not result in an annual effect on the economy of $100,000,000 or more; a major increase in costs or prices; or significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of United States-based companies to compete with foreign-based companies in domestic and export markets.

List of Subjects in 21 CFR Part 1308

• Administrative practice and procedure
• Drug traffic control
• Reporting and recordkeeping requirements

Under the authority vested in the Attorney General by Section 201(a) of the CSA (21 U.S.C. 811(a)), and delegated to the Administrator of the DEA by the Department of Justice regulations (28 CFR 0.100) and re-delegated to the Deputy Administrator pursuant to 28 CFR 0.104, the Acting Deputy Administrator proposes to amend 21 CFR part 1308 as follows:

PART 1308—SCHEDULES OF CONTROLLED SUBSTANCES

1. The authority citation for part 1308 continues to read as follows:

Authority: 21 U.S.C. 811, 812, 871(b) unless otherwise noted.

2. Section 1308.11 is amended by:

A. Redesignating existing paragraphs (d)(15) through (d)(32) as paragraphs (d)(16) through (d)(33),

B. Adding a new paragraph (d)(15),

C. Further redesignating paragraphs (d)(19) through (d)(33) as paragraphs (d)(20) through (d)(34),

D. Adding a new paragraph (d)(19),

E. Removing paragraphs (g)(3) and (g)(4) to read as follows:

§ 1308.11

Schedule I.

* * * * *

(d) * * *

(15) Alpha-methyltryptamine (other name: AMT)—7432.

* * *

(19) 5-methoxy-N,N-diisopropyltryptamine (other name: 5-MeO-DIPT)—7439.

* * * * *

Dated: March 25, 2004.

Michele M. Leonhart,

Acting Deputy Administrator.