Newsgroups: alt.drugs just got done typing this out.. The following is a transcript from _Drugs_And_Behavior_ (Fred Leavit, 1982) (I apoligize for the screwed up numbers of the references, this is because the same section of the book looks into other drugs and puts all of the references to them in the same list, in alphabetical order) LSD AND RELATED HALLUCINOGENS ** Tolerance and Withdrawl Tolerance develops rapidly to LSD, mescaline, and psilocybin, and there is cross tolerance between them. Cross tolerance is not exhibited between these agents and dimethyltryptamine (DMT); and little is known about the development of tolerance to DOM (STP). There are no serious withdrawl symptoms. ** Adverse Effects CHROMOSOME DAMAGE. One of the major concerns about LSD stems from a 1967 paper by Cohen et al. (29) that suggested that LSD damages chromosomes. Cells with damaged chromosomes are potentially dangerous to their bearer, because they may establish cancerous cell lines, and are dangerous to unborn children, because chromosomes carry the genetic message across generations. Dishotsky et al. (36) reviewed the results of 68 studies published between 1967 and 1970, that were concerned with the possibility of LSD-induced chromosome damage. The highlights of their paper are summarized and discussed below, but without the original references. The study by Cohen et al., and several studies which followed it, involved the addition of LSD to cell cultures. There are problems with this approach. First, the process of culturing cells stimulates them to enter a reproductive phase which is abnormal for them. Second, cells in tests tubes are extremely susceptible to chromosome breakage; aspirin, caffeine, water, and changes in temperature or oxygen pressure are some of the many agents which induce breakage of the same order of magnitude as LSD. Third, the type of breakage produced by LSD is different from that caused by known mutagenic or carcinogenic agents. Fourth, intact organisms have evolved metabolic and excretory systems to eliminate harmful substances, but these detoxification mechanisms are not available to cells in test tubes. Thus, cells have typically been exposed to very high doses for prolonged periods of time. Only four studies investigated chromosome breakage rates in humans before and after exposure to LSD. Only one of the studies was positive. Several studies reported higher breakage rates in users than in nonusers but, as has already been discussed ad nauseum, such studies do not allow for causal interpretation. Some unknown factor(s), such as serious childhood illness, may predispose people to chromosome damage ant to take LSD (see p. 176). One obvious factor is that LSD users are likely to use many other drugs as well. An additional problem is that breakage rates have been measured in white blood cells rather than in reproductive cells. Dishotsky et al. pointed out that chromosome damage was much more likely to occur in users of illicit LSD than in volunteers administered known quantities of pure LSD in laboratories. The probable explanation is that illicit LSD contains substantial quantities of adulterants (85 and below), and these may cause breakage. In several cases, breakage rates returned to the normal range withing months of the last dose. As is so disturbingly often the case, the research may tell more about bias in science than about LSD and chromosome damage. Investigators who reported more than one study tended to report the same findings in each. Negative findings may have resulted from small sample size or insensitive testing procedures; for even if LSD affects chromosomes, the effects will not show up unless tested with proper experimental procedures. There is evidence that the negative studies used too few subjects; thus, although only five of fifteen studies yielded statistically significant results,* LSD users had nonsignificant but elevated breakage rates in 10 of the studies. * Statistical significance refers to the probability that observed differences between two or more groups are due to chance factors. Scientists conventionally accept research as being statistically significant if the likelihood that differences are due to chance is less than 1 in 20. If too few subjects are used, the results will not be statistically significant, no matter how strong the drug effect (just as , if a two-headed coin is flipped only four times, the flipper would not be able to conclude on statistical grounds that the coin is biased). Conversely, if huge numbers of subjects are used, even trivial differences will attain statistical significance (which, remember, means only "not due to chance"), but such results may have little scientific significance. There have been studies since the Dishotsky et al. paper. In general, these show no effect of LSD on chromosomes (42, 81, 111, 122). ACUTE PANIC REACTIONS. Not all drug experiences turn out as anticipated. Acute panic reactions, depression, paranoia, and psychotic episodes occur with sufficient frequency to make the phrase "bad trip" and important part of the lexicon of the drug culture. Any potentially enjoyable event may prove to be a disappointment, as when rainy weather spoils a picnic. But the special quality of drug-induced bad trips is that they cannot easily be terminated. Cohen (31) reported that one of 2500 patients taking LSD during psychotherapy committed suicide; and 0.02% of normal subjects who took LSD experimentally experienced psychotic reactions of greater than 24 hours in duration. Louria (82) used the suicide as reason for condemning the therapeutic use of LSD, a position that ignores the possibility that the suicide rate of patients in therapy and not given LSD may be higher than one in 2500. FLASHBACKS. Flashbacks are sudden and unexpected recurrences of aspects of an earlier drug experience. In a study of 2256 Army enlisted men, 23% reported flashbacks from LSD (5% from amphetamine, 1% from marijuana) (132). Flashbacks have not been shown to be dangerous and, in fact, are often self- induced. Matefy et al. (87) quoted one user: "I just call it talking yourself into a flashback.....It's like getting high all over again." PROLONGED PSYCHOTIC REACTIONS. Pradhan and Hollister (103) stated that fewer than 1 per 1000 experimental LSD subjects, and fewer than 2 per 1000 patients who ingest LSD, suffer psychotic reactions lasting longer than 48 hours. Approximately two-thirds of those who do suffer such reactions present a history of psychopathology prior to drug use (11). LSD is often taken in a last-ditch effort to solve and impending crisis which has proven refractory to other attempts at solution (46). If the drug does not help, symptoms may worsen, but not because of the LSD. The data do not justify arguments that LSD is extremely dangerous "because of its capability to induce attempted or completed homicide, attempted suicides, or even prolonged psychosis" (82, p. 254). CEREBRAL DEFICIT. Some authors have reported permanent cerebral deficit in LSD users. Others, however, have disputed the findings (1, 144). In any event, there are no relevant experimental studies, but only comparisons of users with nonusers. ** Benefitial Effects Many users of LSD wax lyrical about its ability to promote insights into everyday problems, to enhance creativity, and to provide mystical and religious experiences. These claims are evaluated in appropriate chapters. REFERENCES 1. Acord, L. & Barker, D. Hallucinogenic drugs and cerebral deficit. J. Nerv. Ment. Dis., 1973, 156: 281-283. 11. Blumenfield, M. & Glickman, L. Ten months experience with LSD users admitted to county psychiatric receiving hospital. NY State J. Med., 1967, 67: 1849 - 1853. 29. Cohen, M., Marinello, M., & Back, N. Chromosomal damage in human leuko- cytes induced by lysergic acid diethylamide, Science, 1967, 155: 1417 - 1419. 31. Cohen, S. Lysergic acid diethylamide: side effects and complications. J. Nerv. Ment. Dis., 1960, 130: 30 - 40. 36. Dishotsky, N. et al. LSD and genetic damage. Science, 1971, 172: 431 - 440. 42. Fernandez, J. et al. LSD. . . an in vivo retrospective chromosome study. Ann. Hum. Genet., 1973, 37: 81 - 91. 46. Glickman, L. & Blumenfield, M. Psychological determinants of "LSD reac- tions." J. Nerv. Ment. Dis., 1967, 145: 79 - 83. 81. Long, S. Does LSD induce chromosomal damage and malformation? A review of the literature. Teratology, 1972, 6: 75 - 90. 82. Louria, D. Abuse of lysergic acid diethylamide--an increasing problem. In Wilson, C. (Ed.) Adolescent Drug Dependence. New York: Pergamon, 1968 85. Marshman, J. & Gibbins, R. The credibility gap in the illicit drug market. Addictionsm 1969, 16: 22 - 25. 87. Matefy, R., Hayes, C., & Hirsch, J. Psychedelic drug flashbacks: Attentional deficits? J. Abnorm. Psych., 1979, 88: 212 - 215. 95. Naditch, M. Acute adverse reactions to psychoactive drugs, drug usage, and psychopathology. J. Abnorm. Psych., 1974, 83: 394 - 403. 103. Pradhan, S. & Hollister, L. Abuse of LSD and other hallucinogenic drugs. In Drug Abuse: Clinical Aspects and Basic Aspects. St. Louis: Mosby, 1977. 111. Robinson, J. et al. Chromosome aberrations and LSD: A controlled study in 50 psychiatric patients. Br. J. Psychiatr., 1974, 125: 238 - 244 122. Simmons, J., Sparkes, R., & Blake, P. Lack of chromosomal damaging effects by moderate doses of LSD in vivo. Clin. Genet., 1974, 5: 59 - 61. 125. Smith, D. & Mehl, C. An analysis of marijuana toxicity. In Smith, E. (Ed.) The New Social Drug. Englewood Cliffs, N.J.: Prentice-Hall, 1970. 132. Stanton, M. & Bardoni, A. Drug flashbacks: Reported frequency in a military population. Am. J. Psychiatr., 1972, 129: 751 - 755. 144. Wright, M. & Hogan, T. Repeated LSD ingestion and performance on neuro- psychological tests. J. Nerv. Ment. Dis., 1972: 432 - 438. .