References and Notes

1. R. W. Holley, J. Apgar, G. A. Everett, J. T.Madison, M. Marquisee, S. H. Merrill, J. R.Penswick, A. Zamir, Science 147, 1462(1965).

2. H. Zachau, D. Dutting, H. Feldman, Angew.Chem. 78, 392 (1966); J. T. Madison, G. A.Everett, H. Kung, Science 153, 531 (1966);U. L. Rajbhandary, S. H. Chang, A. Stuart,R. D. Faulkner, R. M. Hoskinson, H. G.Khorana, Proc. Nat. Acad. Sci. U.S. 57,751 (1967).

3. Abbreviations: Ap, adenosine 3'-phosphate;Cp, cytidine 3'-phosphate; DiHUp, 5,6 di-hydrouridine 3'-phosphate; DiMeGp, N2-dimethylguanosine 3'-phosphate; Ip, inosine3'-phosphate; MeGp, 1-methylgaunosine 3'-phosphate; MeIp, 1-methylinosine 3'-phos-phate; y,p, pseudouridine 3'-phosphate; V!,pseudouridine 2', 3' cyclic phosphate; Tp,ribothymidine 3'-phosphate; tRNA, transferRNA; Up, uridine 3'-phosphate.

4. P. T. Gilham, J. Amer. Chem. Soc. 84, 687(1962); S. W. Brostoff and V. M. Ingram,Fed. Proc. 26, 733 (1967).

5. G. Augusti-Tocco and G. L. Brown, Nature206, 683 (1965); P. G. Knorre, E. G. Maly-

not accentuated by chlorpromazine.

A new hallucinogenic drug, STP,has been used extensively by "hippie"populations in recent months. Therehave been reports that this drug pro-duces hallucinogenic reactions lastingup to 72 hours and that these reactionsare intensified by chlorpromazine, thetranquilizer commonly used as an anti-dote to other hallucinogens. Chemistsat the U.S. Food and Drug Administra-tion have identified black-market prep-arations of STP as identical with DOM(2,5-dimethoxy-4-methyl-amphetamine)and have estimated -that black-marketpreparations of this drug contain about10 mg of DOM in each pill (1). Toclarify the effects of DOM in man, wehave, at the request of the Food andDrug Administration, examined thephysical and mental actions of DOMin normal control volunteers. Two in-dependent studies have been performed,one at the Johns Hopkins Hospital inBaltimore and one at the Veterans Ad-ministration Hospital in Palo Alto,California.

Five normal control male volunteersaged 21 to 35 were obtained through3 NOVEMBER 1967

gin, G. S. Mushinskaya, V. V. Favorov,Biol. Chem. 237, 798 (1962).

6. R. Naylor, N. W. Y. Ho, P. T. Gilham,J. Amer. Chem. Soc. 87, 4209 (1965).

7. J. Apgar, R. W. Holley, S. H. Merrill, J.Biol. Chem. 237, 798 (1962).

8. V. M. Ingram and J. A. Sjoquist, ColdSpring Harbor Symp. Quant. Biot. 28, 117(1963).

9. V. M. Ingram and J. G. Pierce, Biochemistry1, 580 (1962).

10. A. Armstrong, H. Hagopian, V. M. Ingram,E. K. Wagner, ibid. 5, 3027 (1966).

11. J. A. Nelson and R. W. Holley, Fed. Proc.26, 733 (1967).

12. Up* is a mixture of Up and diHUp [seeHolley et al. (1)].

13. J. R. Penswick and R. W. Holley, Proc.Nat. Acad. Sci. U.S. 53, 543 (1965).

14. W. M. Stanley and R. M. Bock, Anal. Bio.chem. 13, 43 (1965).

15. R. W. Holley, J. Apgar, G. A. Everett, J. T.Madison, S. H. Merrill, A. Zamir, ColdSpring Harbor Symp. Quant. Biol. 28, 117(1963).

16. Supported by USPHS Grant AM-083090.S. W. Brostoff was supported by a USPHSfellowship.

24 July 1967

the office of financial aid at the JohnsHopkins University. They were inter-viewed by an experienced clinical psy-chiatrist (L.F.) and were administereda Minnesota Multiphasic Personalityinventory and a Thematic Appercep-tion Scale. Applicants with a historyof frequent use of marijuana or othermental stimulants were rejected. Be-fore receiving the drug, each subjectwas given a physical examination,chest x-ray, electrocardiogram, electro-encephalogram, tests of blood chemis-try, and hematological tests. Subjectswere told that they would receive adrug called DOM, which was presum-ably identical to the hallucinogen STP,but that their dose would be consider-ably smaller than that thought to oc-cur in STP tablets.

At 9 a.m., after fasting since thepreceding midnight, subjects receivedDOM at dosages of 2.0, 2.4, 2.4, 2.8,and 3.2 mg as the hydrochloride dis-solved in distilled water. Before receiv-ing the drug and 2, 4, and 6 hoursthereafter, tests of free recall, associa-tive organization, subjective mood

scales, and an LSD symptom specificscale were administered. Results ofthese tests will be reported separately(2). Urine collections before adminis-tration of the drug and 3, 6, 9, and 24hours thereafter were assayed for un-changed DOM by a specific and sensi-tive spectrophotofluorometric method(3). At hourly intervals, pulse, bloodpressure, oral temperature, and pupillarydiameter were measured. Interviewswith subjects were tape-recorded atvarious intervals.

Pupillary dilatation of about 15 per-cent occurred between 1 and 6 hoursafter administration of the drug. Pulserate increased (mean increase of 15beats per minute) as did systolic bloodpressure (mean increase of 15 mm-Hg)between 1 and 6 hours, with a maxi-mum effect at 4 hours; however, dia-stolic blood pressure was unaffected.The mean oral temperature had in-creased by a maximum of 1.20F 4hours after administration of the drug.

Certain features were common tothe experiences of all five subjects. Sub-jective effects began between 1 and 2hours after administration of the drug,with a peak between 3 and 5 hours andsubsidence of effects by 7 to 8 hours.All subjects initially experienced amoderate euphoria. Perceptual effectsvaried but were present to some de-gree in all.The subject who received 2.0 mg

had the mildest reaction. He began tofeel "a little high" 2 hours after takingthe drug. At 3 hours he felt "a littleweird; there is like a blank space be-tween my head and body." Four hoursafter taking the drug, he felt normaland described his experience, "I feltgood, more than usual. With my eyesclosed I was pretty relaxed, and therewas lots of visual imagery while listen-ing to music. . . . It is like a half-waydecent pot experience."The three subjects who received 2.4

and 2.8 mg experienced effects similarto those described above, but the maxi-mum effects lasted until 5 hours afterthe drug was taken; the effects hadsubsided by 8 hours. One of the sub-jects who received 2.4 mg first felt achange 1.5 hours after taking the drug,when he noticed that things on thewall were slightly shifting and surfaceswere rippling. He described it, "Thingswere creeping, waving, a sort of corru-gated effect. . . . I felt a little light-headed and high. . . . Sometimes theceiling had patterns of dots whichturned into real faces . . . and when Iclosed my eyes it was like dreaming

669

2,5-Dimethoxy-4-methyl-amphetamine (STP):A New Hallucinogenic Drug

Abstract. We have assessed the effects in normal control volunteers of 2,5-dimethoxy-4-methyl-amphetamine, the chemical present in the hallucinogenicdrug STP, in two independent trials. In low doses, this compound produces a mildeuphoria. Doses greater than 3 milligrams may cause pronounced hallucinogeniceffects lasting about 8 hours and similar to those produced by hallucinogenicdoses of lysergic acid diethylamide, mescaline, and psilocybin. 2,5-Dimethoxy-4-methyl-amphetamine, which is chemically related to mescaline and ampheta-mine, is about 100 times more potent as a hallucinogen than mescaline and onlyone-thirtieth as potent as lysergic acid diethylamide. Its psychological effects are

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while awake. . . . The whole situationseems rather funny. I'm cheerful,gay, exhilarated."The subject who received 3.2 mg ex-

perienced a pronounced hallucinogeniceffect like that which might occur aftertaking a hallucinogenic dose of lyser-gic acid diethylamide (LSD). Ten hoursafter taking the drug, he described thepreceding experience, "The first effectcame during lunch (2 hours after ad-ministration of the drug) when I startedstaring at the orange sherbet whichwas beautiful, brilliant orange, fallingdisorganizedly like a whirlpool.Later (5 hours after taking the drug).I began shrinking, and water in theglass on the taible was getting biggerand moving toward me, coming to en-velop me. . . I was really scared.. . . I saw a witch doctor, then a horseon the wall. . . Then the ceilingstarted moving up and down and waspurple and yellow. . I felt I waslosing control." Although this subjectwas "coming down" at 7 hours andslept well that night after receivintgglutethimide (0.5 g), he reported laterthat the next day he felt a mild eupho-ria alternating with depression. Noother subject reported any lasting ef-fects.

Regardless of the dose of DOM,about 20 percent of the ingested doseappeared in the urine within 24 hoursas the unchanged compound. Therewas a definite peak of urinary excre-tion {between 3 and 6 hours after ad-ministration of the drug; this peakcorresponded to the peak clinical ef-fects. If urinary excretion reflectsplasma concentration, this finding sug-gests that DOM may be slowly ab-sorbed into the circulation and thatclinical effects are related to plasmaconcentrations of the unchanged drug.Aghajanian and Bing (4) have describeda similar relationship between plasmaconcentration and mental effects ofLSD.

In the Palo Alto study, 16 nornmalcontrol male and female volunteers re-ceived between 2 and 14 mg of DOMas the hydrochloride in capsules withlactose filler after fasting since the pre-vious night. The individual doses werein milligrams: 2. 3. 4, 5, 6, 8, 9. 10. 1,12, 13. and 14. Two subjects receivedeach of the 8. 10. and 12 mg dosages.A mood scale and psychometric mea-sures (number facility test and flexibilityof closure test) were administered be-fore the drug was administered and 1,3, and 5 hours after it was given. Asymptom-sign questionnaire for hallu-

670

cinogenic effects was completed by eachsubject after su'bsidence of drug effects.At 2, 4, and 8 hours after administra-tion of the drug, pupillary diameter,deep tendon reflexes, blood pressure,pulse rate, and oral temperature weremeasured. Blood specimens were col-lected at 2, 4, and 8 hours for deter-mination of free fatty-acid and glucoseconcentrations.

In the lowest doses, DOM producedmild euphoric effects. Doses in excessof 5 mg always produced marked hallu-cinogenic effects whose intensity andduration were related to the dose. Ef-fects began about I hour after admin-istration of the drug, with a peak be-tween 3 and 5 hours and subsidenceby 7 to 8 hours. There were no per-sistent effects the next day, except inone subject who reported a mild eupho-ria the next morning.

Frequency and intensity of responseson the symptom-sign questionnaire suni-marize the clinical syndrome producedby DOM. The somatic changes includ-ed nausea, sweating, paresthesia, andtremors: perceptual changes comprisedblurred vision, multiple images, vibra-tion of objects, visual hallucinations,distorted shapes, enhancement of de-tails, slowed passage of time, and in-creased contrasts. With respect to psy-chic effects the subjects reported thatthey were happy, that they lost controlof thoughts at times, that they had dif-ficulty in expressing self, that the mindwas flooded with thoughts, that themind was occasionally blank, and thatthey were easily distracted. Subjectsseemed to have good meniory fordrug experience.

There was some increase in pulserate (mean increase of 25 beats perminute) and systolic blood pressure(niean increase of 28 mm-Hg) withpeak effects at 4 hours; diastolic bloodpressure was unaffected. The mean in-crease in pupillary diameter was 15percent at 2 and 4 hours. Althoughthe glucose concentration in blood wasunchanged, free fatty acids in the plas-ma doubled 4 hours after the admin-istration of DOM.

Three subjects simultaneously re-ceived oral doses of chlorpromazine(200 mg) and DOM (10. 12. or 14 mg).All three subjects had hallucinogenicreactions which, however, appeared lesspronounced than those in subjects whoreceived the same doses without chlor-promazine. These subjects were alsovery drowsy. There was no accentua-tion of any DOM effects by chlorpro-mazine.

It has been rumored that chemicallypure STP is more potent on a weightbasis than LSD. Our studies indicatethat DOM is a potent hallucinogenicagent able to produce hallucinogeniceffects in doses greater than 3 mg anda mild euphoria in lower doses. Thiscompound is chemically related to mes-caline, the minimum hallucinogenicdose of which is about 300 mg in anadult. Thus, DOM is about 100 timesmore potent than mescaline. Since theminimum hallucinogenic dose for LSDis about 0.1 mg, DOM is only aboutone-thirtieth as potent as LSD.

It has been reported in the newsmedia that effects of STP may persistfor 72 hours and are intensified bychlorpromazine, which usually attenu-ates effects of hallucinogenic drugs.Only two of our 25 subjects reportedeffects persisting into the following day,and none was affected 2 days later,even though doses as high as 14 mg,more than the average amount of DOMin black-market STP pills, were ad-ministered.

It is possible that those of the "hip-pie" population who developed pro-longed reactions to STP had beensensitized by previous experiences withhallucinogenic drugs. In the Palo Altostudy chlorpromazine appeared to at-tenuate the effects of DOM in threesubjects and definitely did not intensifythem as had been reported in STPusers. In our studies, chloripromazinewas administered simultaneously withDOM, while it has been given to STPusers after they have already been on"bad trips." It is also possible thatusers of STP who developed prolongedadverse reactions accentuated by chlor-promazine had taken a drug other thanDOM. Adverse reactions to atropineand related compounds may be intensi-fied by chlorpromazine.

SOLOMON H. SNYDERLouis FAILLACE

Departtmenits of Pharmzacology andPsychiatry, Johns HopkinsUniversity School of Medicine,Baltimore, Maryland 21205

LEO HOLLISTERVeterans A dministration Hospital,Palo Alto, California 94304

References and Notes

1. M. Joffe, personal communication.2. H. Weingartner, S. Snyder, L. Faillace, in

preparation.I S.SSnyder and A. Sangavi, in preparation.4. G. Aghajanian and 0. H. L. Bing, Cliti. Phar-

niacol. Therap. 5, 611 (1964).5. Supported by FDA contract 68.8. S.S. is a

recipient of NIMH research career develop-ment award K-3-MH-33128.

6 October 1967

SCIENCE, VOL. 158

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