29 April 19>2p.5>2p0>1p, 52-D COMPARISON OF EFFECTS >1p6>1pF C>1p-9 DISSOLVED IN OIL WITH THOSE OF C>1p-9 DISSOLVED IN ALCOHOL. PURPOSE: To determine if C>1p-9 dissolved In oil is as active as C>1p-9 dissolved In alcohol and administered dispersed in watery solution, >2pM>2pETHODS>1p: Subjects: Five nontolerant former morphine addicts, all 2 male, who were serving sentences for violation of the federal narcotic laws were used in these experiments. All were phys>2pi>2p->1p.ally healthy, presented no evidence of the major psychoses, and all had experienced the effects of marihuana in a free environment. Drugs: All drugs wer>2pe given at >1p8 a.m. with the patients fasting. C>1p-9 was available as a solution containing >1p1>1p0 mg/ml in vegetable oil In perles>1p. The perl2es were opened, the doses measured and diluted with >1p8 cc of vegeta>2pb le oil >1p(>1p">2p,>2pMazo>2pla>1p">1p)>1p. The glass was r>2p@nsed with 2 additional portions of 4 cc of oil. Vegetable oil containing no drug was used as a placebo. C>1p-9 was also available as a solution of >1p1 m>2p.g>1p/m>2pi in 95 per cent ethanol. The dose was measured and diluted with >1p8 cc of distilled water, forming a milky suspension. The glass was rinsed 9with two portions of water. Page 2 Design: -The patients received at weekly intervals, in a randomized, balanced order, the following drugs: >1p1>2p*>1p0 and >1p1>1p.>1p5 mg per 70 kg of C>1p-9>1p->2pin oil; >1p1>1p.>1p0 and >1p1>1p.>1p5 mg>1p/70 kg of C>1p-9 In alcohol; and a>2p.placebo>1p, The patients were unaware of the Identity of the drugs ('single-blind" procedure). Observati2ons: The following observations were made at hourly intervals twice before and eight times after the drugs: pulse rate and blood pressure after>1p.ten minutes rest in bed, pulse rate and blood pressure after arising from bed and standing quietly for one minute, and rectal temperature. In addition, patients completed a questionnaire containing 67 items at hourly intervals.-once before and eight times after the drug. Analys_>2pi2s>1p: In-the cases of r>2pectal temperature, resting and standing pulse rates, and resting and standing blood pressures, the values at each hour after the drug were subtracted from the average of the p>2pr>2p.edrug observations. These values >2pf>2p-or change from control constituted time-action curves, so the are as under these curves were calculated and the usual statistical calcula>2p- tions made using the t>1p-test for paired observati4ons. Questions. scored positively after the drugs were counted over the entire post-drug period, eliminating answers also scored-positively prior to the drug. Page RESULTS The results are su>2pm>2pmarized In table >1p1>1p. All doses of C>1p-9 In both alcohol and-oil co>2pnsistently elevated resting and standing pulse rates, decreased the usual rise In r>2pi>2p@st>1ping blood >1p0 pressure, and caused postural hypertension; Rectal temperature 2 was not consistently affected. In general, C>1p-9 dissolved in alcohol was consistently more effective than C>1p-9 disso>2pl>2pted in oil, thought the d>1piffer>2p.ences did not reach statistical significance, There was no significant difference in onset and peak time of the changes in pulse rate and standing blood pressures. The usual subjective reports >2p->2p->1p- change In mood, mild perceptual distortion dry mouth, di2zziness and sleepiness >1p->1p- were reported after both oily and alcoholic solutions. Four of >1p5 patient>2ps f>2painted on standi>2png after >1p1>1p.>1p5 mg of >2pC>1p-9 in alcohol, whereas only one of >1p5 fainted after >1p1>1p.>1p5 mg of >2pC>1p-9 in oil. One pat>2pi>1p'ent fainted after >1p1>1p.>1p0 mg In alcohol., and none after >1p1>1p.>1p0 mg in alcohol. Conclusion: C>1p-9 dissolved In oil is effective In inducing 4 postural hypertension and marihuana-like subjective effects, but is probably less effective than C>1p-9 in alcohol. Table >1p1>1p. 52-D Comparison of Effects of C>1p-9 In Alcohol with Those >2pI>2pI Oil. n t>2p%>2piEASURE DOSE AND VEHICLE 2 Placebo Oil Alcohol Oil Alcohol >2p->1p(Oi >2p1>1p) >1p(>1p1>1p.>1p0 mg) >2p(>2p1>1p.>2p0 mg)' >1p(>2pI >1p.>1p5 mg) >1p(>1p1>2p->1p5 mg) Resting Pulse Rate >1p+45>1p.6 ñ 19 >1p+51>1p.6 ñ 16>1p.5 >1p+63>1p.6 ñ >1p1>1p8 >1p+72>1p.8 ñ 10>1p.3 9>1p4>2p-3 ñ 19>1p.6 2 St ling Pulse Rate >1p-10>1p.2 ñ 30>2p.9 >2p+8>2pi>1p.6 ñ 36 >1p+95>2p->2p->2pi>2p- ñ >2p45>1p.6 >1p+87>2p.1 ñ 25>2p.8 >2p+118>1p.7 >2p:t >2p46 Resting Blood Pressure >1p+64>2p-8 ñ 33>1p.6 >1p+>1p1>1p5>2p.>1p0 ñ 33 >1p+3>1p1>2p.9 ñ >1p1>1p8 >1p+34>1p.3 ñ >2p1>1p1>1p.>1p5 >1p+22>2p.7 ñ>2p,17>2p.8 Standing Blood Pressure >1p+40>1p.1 ñ >1pI>2ph>1p.>1p.8 >1p+19>1p.23 ñ 35 >2p.>1p-38>2p.8 ñ 34>2p.>1p1 >1p-93>2p-4 ñ 23>1p.2 >1p->2pi>2pio>1p.6 ñ 39>2p.5 Te>2pmperature >1p+ 1>1p.9 >2pñ 0>1p.6 >1p+ 2>2p.>1pL>2pi>2p, ñ 0>2p-35 >1p+ >1p1>2p-4 ñ >1p0>2p.>1p5 +. 0>1p.9 ñ 0>1p.9 >1p+ 1>1p.0>2p4 ñ 0>1p.2 Number of Positive >2pi>1p.6 ñ 1>1p.2 >1p1>1p1>1p.>1p0 ñ >2p4>1p.2 >1p1>1p1>2p.>1p0 ñ 3>2p.1 >1p8>2p.>1p0 ñ 3>2p-1 18>21p.2 6>1p.55 Responses on >2pQ>1pu>1pe>1ps>1pt>2pi>1po>1pn>1pn>2pa>2pi>1pr>1pe Figures are the>1p.means >1p(>1p5 subjects) of areas under the time-action curves for the various measures >1p(>2p"be>1p'at>1p-hours>2p,>1p" >1p"mm>1p-hours>1p,>1p'>2p@>2p' etc., except In case of 'number of positive responses on the questionnaire). A positive sign Indicates an Increase In the measurements a 0 negative sign a dec>2prease>2p*